Abstract
The interaction between intracellular bacterial pathogens with the host immune response can result in multiple outcomes that range from asymptomatic clearance to the establishment of infection. At its core, these interactions result in multiple metabolic adaptations of both the pathogen and its host cell. There is growing evidence that the host metabolic response plays a key role in the development of immune responses against the invading pathogen. However, successful intracellular pathogens have developed multiple mechanisms to circumvent the host response to thrive in the intracellular compartment. Here, we provide a brief overview on the crucial role of fundamental metabolic host responses in the generation of protective immunity to intracellular bacterial pathogens and discuss some of the mechanisms used by these pathogens to exploit the host metabolic response to their own advantage. This understanding will further our knowledge in host-pathogen interactions and may provide new insights for the development of novel therapies.
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References
Adams LB, Dinauer MC, Morgenstern DE, Krahenbuhl JL (1997) Comparison of the roles of reactive oxygen and nitrogen intermediates in the host response to Mycobacterium tuberculosis using transgenic mice. Tuber Lung Dis 78(5–6):237–246. https://doi.org/10.1016/S0962-8479(97)90004-6
Alfano M, Graziano F, Genovese L, Poli G (2013) Macrophage polarization at the crossroad between HIV-1 infection and cancer development. Arterioscler Thromb Vasc Biol 33(6):1145–1152. https://doi.org/10.1161/ATVBAHA.112.300171
Allegra S, Leclerc L, Massard PA, Girardot F, Riffard S, Pourchez J (2016) Characterization of aerosols containing Legionella generated upon nebulization. Sci Rep 6:33998. https://doi.org/10.1038/srep33998
Anderson CJ, Kendall MM (2017) Salmonella enterica Serovar Typhimurium strategies for host adaptation. Front Microbiol 8:1983. https://doi.org/10.3389/fmicb.2017.01983
Antunes LC, Arena ET, Menendez A, Han J, Ferreira RB, Buckner MM, Lolic P, Madilao LL, Bohlmann J, Borchers CH, Finlay BB (2011) Impact of salmonella infection on host hormone metabolism revealed by metabolomics. Infect Immun 79(4):1759–1769. https://doi.org/10.1128/IAI.01373-10
Ao TT, Feasey NA, Gordon MA, Keddy KH, Angulo FJ, Crump JA (2015) Global burden of invasive nontyphoidal Salmonella disease, 2010(1). Emerg Infect Dis 21(6):941. https://doi.org/10.3201/eid2106.140999
Armstrong JA, Hart PD (1971) Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med 134(3 Pt 1):713–740. https://doi.org/10.1084/jem.134.3.713
Asrat S, Dugan AS, Isberg RR (2014) The frustrated host response to Legionella pneumophila is bypassed by MyD88-dependent translation of pro-inflammatory cytokines. PLoS Pathog 10(7):e1004229. https://doi.org/10.1371/journal.ppat.1004229
Azad AK, Sadee W, Schlesinger LS (2012) Innate immune gene polymorphisms in tuberculosis. Infect Immun 80(10):3343–3359. https://doi.org/10.1128/IAI.00443-12
Bachmann NL, Polkinghorne A, Timms P (2014) Chlamydia genomics: providing novel insights into chlamydial biology. Trends Microbiol 22(8):464–472. https://doi.org/10.1016/j.tim.2014.04.013
Bai X, Feldman NE, Chmura K, Ovrutsky AR, Su WL, Griffin L, Pyeon D, McGibney MT, Strand MJ, Numata M, Murakami S, Gaido L, Honda JR, Kinney WH, Oberley-Deegan RE, Voelker DR, Ordway DJ, Chan ED (2013) Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages. PLoS One 8(4):e61925. https://doi.org/10.1371/journal.pone.0061925
Baker RG, Hayden MS, Ghosh S (2011) NF-kappaB, inflammation, and metabolic disease. Cell Metab 13(1):11–22. https://doi.org/10.1016/j.cmet.2010.12.008
Barry KC, Fontana MF, Portman JL, Dugan AS, Vance RE (2013) IL-1alpha signaling initiates the inflammatory response to virulent Legionella pneumophila in vivo. J Immunol 190(12):6329–6339. https://doi.org/10.4049/jimmunol.1300100
Blumenthal A, Nagalingam G, Huch JH, Walker L, Guillemin GJ, Smythe GA, Ehrt S, Britton WJ, Saunders BM (2012) M. tuberculosis induces potent activation of IDO-1, but this is not essential for the immunological control of infection. PLoS One 7(5):e37314. https://doi.org/10.1371/journal.pone.0037314
Boman J, Hammerschlag MR (2002) Chlamydia pneumoniae and atherosclerosis: critical assessment of diagnostic methods and relevance to treatment studies. Clin Microbiol Rev 15(1):1–20
Bowman CC, Bost KL (2004) Cyclooxygenase-2-mediated prostaglandin E2 production in mesenteric lymph nodes and in cultured macrophages and dendritic cells after infection with Salmonella. J Immunol 172(4):2469–2475
Bresciani G, da Cruz IB, Gonzalez-Gallego J (2015) Manganese superoxide dismutase and oxidative stress modulation. Adv Clin Chem 68:87–130. https://doi.org/10.1016/bs.acc.2014.11.001
Brothwell JA, Muramatsu MK, Toh E, Rockey DD, Putman TE, Barta ML, Hefty PS, Suchland RJ, Nelson DE (2016) Interrogating genes that mediate Chlamydia trachomatis survival in cell culture using conditional mutants and recombination. J Bacteriol 198(15):2131–2139. https://doi.org/10.1128/JB.00161-16
Buck MD, O’Sullivan D, Pearce EL (2015) T cell metabolism drives immunity. J Exp Med 212(9):1345–1360. https://doi.org/10.1084/jem.20151159
Byrne B, Swanson MS (1998) Expression of Legionella pneumophila virulence traits in response to growth conditions. Infect Immun 66(7):3029–3034
Byrne GI (2010) Chlamydia trachomatis strains and virulence: rethinking links to infection prevalence and disease severity. J Infect Dis 201(Suppl 2):S126–S133. https://doi.org/10.1086/652398
Calder PC (2013) Feeding the immune system. Proc Nutr Soc 72(3):299–309. https://doi.org/10.1017/S0029665113001286
Carabeo RA, Mead DJ, Hackstadt T (2003) Golgi-dependent transport of cholesterol to the Chlamydia trachomatis inclusion. Proc Natl Acad Sci USA 100(11):6771–6776. https://doi.org/10.1073/pnas.1131289100
Cardoso MS, Silva TM, Resende M, Appelberg R, Borges M (2015) Lack of the transcription factor Hypoxia-Inducible Factor 1alpha (HIF-1alpha) in macrophages accelerates the necrosis of Mycobacterium avium-induced granulomas. Infect Immun 83(9):3534–3544. https://doi.org/10.1128/IAI.00144-15
Casanova JE (2017) Bacterial autophagy: offense and defense at the host-pathogen interface. Cell Mol Gastroenterol Hepatol 4(2):237–243. https://doi.org/10.1016/j.jcmgh.2017.05.002
Cascales E (2017) Inside the chamber of secrets of the Type III secretion system. Cell 168(6):949–951. https://doi.org/10.1016/j.cell.2017.02.028
Castillo EF, Dekonenko A, Arko-Mensah J, Mandell MA, Dupont N, Jiang S, Delgado-Vargas M, Timmins GS, Bhattacharya D, Yang H, Hutt J, Lyons CR, Dobos KM, Deretic V (2012) Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc Natl Acad Sci USA 109(46):E3168–E3176. https://doi.org/10.1073/pnas.1210500109
Chambers MC, Song KH, Schneider DS (2012) Listeria monocytogenes infection causes metabolic shifts in Drosophila melanogaster. PLoS One 7(12):e50679. https://doi.org/10.1371/journal.pone.0050679
Chang CH, Curtis JD, Maggi LB Jr, Faubert B, Villarino AV, O’Sullivan D, Huang SC, van der Windt GJ, Blagih J, Qiu J, Weber JD, Pearce EJ, Jones RG, Pearce EL (2013) Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153(6):1239–1251. https://doi.org/10.1016/j.cell.2013.05.016
Chen AL, Johnson KA, Lee JK, Sutterlin C, Tan M (2012) CPAF: a Chlamydial protease in search of an authentic substrate. PLoS Pathog 8(8):e1002842. https://doi.org/10.1371/journal.ppat.1002842
Cherayil BJ, McCormick BA, Bosley J (2000) Salmonella enterica serovar typhimurium-dependent regulation of inducible nitric oxide synthase expression in macrophages by invasins SipB, SipC, and SipD and effector SopE2. Infect Immun 68(10):5567–5574
Chico-Calero I, Suarez M, Gonzalez-Zorn B, Scortti M, Slaghuis J, Goebel W, Vazquez-Boland JA, European Listeria Genome C (2002) Hpt, a bacterial homolog of the microsomal glucose- 6-phosphate translocase, mediates rapid intracellular proliferation in Listeria. Proc Natl Acad Sci USA 99(1):431–436. https://doi.org/10.1073/pnas.012363899
Choy A, Dancourt J, Mugo B, O’Connor TJ, Isberg RR, Melia TJ, Roy CR (2012) The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science 338(6110):1072–1076. https://doi.org/10.1126/science.1227026
Cianciotto NP (2001) Pathogenicity of Legionella pneumophila. Int J Med Microbiol 291(5):331–343. https://doi.org/10.1078/1438-4221-00139
Cocchiaro JL, Kumar Y, Fischer ER, Hackstadt T, Valdivia RH (2008) Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole. Proc Natl Acad Sci USA 105(27):9379–9384. https://doi.org/10.1073/pnas.0712241105
Cooper AM, Magram J, Ferrante J, Orme IM (1997) Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J Exp Med 186(1):39–45. https://doi.org/10.1084/jem.186.1.39
Czyz DM, Potluri LP, Jain-Gupta N, Riley SP, Martinez JJ, Steck TL, Crosson S, Shuman HA, Gabay JE (2014) Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens. MBio 5(4):e01534-01514. https://doi.org/10.1128/mBio.01534-14
Dalebroux ZD, Edwards RL, Swanson MS (2009) SpoT governs Legionella pneumophila differentiation in host macrophages. Mol Microbiol 71(3):640–658. https://doi.org/10.1111/j.1365-2958.2008.06555.x
Dandekar T, Fieselmann A, Fischer E, Popp J, Hensel M, Noster J (2014) Salmonella-how a metabolic generalist adopts an intracellular lifestyle during infection. Front Cell Infect Microbiol 4:191. https://doi.org/10.3389/fcimb.2014.00191
DeBerardinis RJ, Thompson CB (2012) Cellular metabolism and disease: what do metabolic outliers teach us? Cell 148(6):1132–1144. https://doi.org/10.1016/j.cell.2012.02.032
Deretic V, Delgado M, Vergne I, Master S, De Haro S, Ponpuak M, Singh S (2009) Autophagy in immunity against Mycobacterium tuberculosis: a model system to dissect immunological roles of autophagy. Curr Top Microbiol Immunol 335:169–188. https://doi.org/10.1007/978-3-642-00302-8_8
Derre I, Swiss R, Agaisse H (2011) The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites. PLoS Pathog 7(6):e1002092. https://doi.org/10.1371/journal.ppat.1002092
Desai M, Fang R, Sun J (2015) The role of autophagy in microbial infection and immunity. Immunotargets Ther 4:13–26. https://doi.org/10.2147/ITT.S76720
Edwards RL, Dalebroux ZD, Swanson MS (2009) Legionella pneumophila couples fatty acid flux to microbial differentiation and virulence. Mol Microbiol 71(5):1190–1204. https://doi.org/10.1111/j.1365-2958.2009.06593.x
Ehrt S, Schnappinger D, Bekiranov S, Drenkow J, Shi S, Gingeras TR, Gaasterland T, Schoolnik G, Nathan C (2001) Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase. J Exp Med 194(8):1123–1140
Eisenreich W, Heesemann J, Rudel T, Goebel W (2013) Metabolic host responses to infection by intracellular bacterial pathogens. Front Cell Infect Microbiol 3:24. https://doi.org/10.3389/fcimb.2013.00024
Eisenreich W, Heesemann J, Rudel T, Goebel W (2015) Metabolic adaptations of intracellullar bacterial pathogens and their mammalian host cells during infection (“Pathometabolism”). Microbiol Spectr 3(3). https://doi.org/10.1128/microbiolspec.MBP-0002-2014
Elks PM, Brizee S, van der Vaart M, Walmsley SR, van Eeden FJ, Renshaw SA, Meijer AH (2013) Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism. PLoS Pathog 9(12):e1003789. https://doi.org/10.1371/journal.ppat.1003789
Elwell C, Mirrashidi K, Engel J (2016) Chlamydia cell biology and pathogenesis. Nat Rev Microbiol 14(6):385–400. https://doi.org/10.1038/nrmicro.2016.30
Elwell CA, Jiang S, Kim JH, Lee A, Wittmann T, Hanada K, Melancon P, Engel JN (2011) Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS Pathog 7(9):e1002198. https://doi.org/10.1371/journal.ppat.1002198
Escoll P, Rolando M, Gomez-Valero L, Buchrieser C (2013) From amoeba to macrophages: exploring the molecular mechanisms of Legionella pneumophila infection in both hosts. Curr Top Microbiol Immunol 376:1–34. https://doi.org/10.1007/82_2013_351
Escoll P, Song OR, Viana F, Steiner B, Lagache T, Olivo-Marin JC, Impens F, Brodin P, Hilbi H, Buchrieser C (2017) Legionella pneumophila modulates mitochondrial dynamics to trigger metabolic repurposing of infected macrophages. Cell Host Microbe 22(3):302–316. https://doi.org/10.1016/j.chom.2017.07.020
Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA (2012) Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 379(9835):2489–2499. https://doi.org/10.1016/S0140-6736(11)61752-2
Fields BS, Benson RF, Besser RE (2002) Legionella and Legionnaires’ disease: 25 years of investigation. Clin Microbiol Rev 15(3):506–526
Fonseca MV, Swanson MS (2014) Nutrient salvaging and metabolism by the intracellular pathogen Legionella pneumophila. Front Cell Infect Microbiol 4:12. https://doi.org/10.3389/fcimb.2014.00012
Fraga AG, Barbosa AM, Ferreira CM, Fevereiro J, Pedrosa J, Torrado E (2017) Immune-evasion strategies of mycobacteria and their implications for the protective immune response. Curr Issues Mol Biol 25:169–198. https://doi.org/10.21775/cimb.025.169
Friedman H, Yamamoto Y, Klein TW (2002) Legionella pneumophila pathogenesis and immunity. Semin Pediatr Infect Dis 13(4):273–279. https://doi.org/10.1053/spid.2002.127206
Gal-Mor O, Boyle EC, Grassl GA (2014) Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ. Front Microbiol 5:391. https://doi.org/10.3389/fmicb.2014.00391
Gillmaier N, Gotz A, Schulz A, Eisenreich W, Goebel W (2012) Metabolic responses of primary and transformed cells to intracellular Listeria monocytogenes. PLoS One 7(12):e52378. https://doi.org/10.1371/journal.pone.0052378
Hackstadt T, Rockey DD, Heinzen RA, Scidmore MA (1996) Chlamydia trachomatis interrupts an exocytic pathway to acquire endogenously synthesized sphingomyelin in transit from the Golgi apparatus to the plasma membrane. EMBO J 15(5):964–977
Haferkamp I (2017) Crossing the border – solute entry into the chlamydial inclusion. Int J Med Microbiol. https://doi.org/10.1016/j.ijmm.2017.08.006
Ham H, Sreelatha A, Orth K (2011) Manipulation of host membranes by bacterial effectors. Nat Rev Microbiol 9(9):635–646. https://doi.org/10.1038/nrmicro2602
Harrison TG, Doshi N, Fry NK, Joseph CA (2007) Comparison of clinical and environmental isolates of Legionella pneumophila obtained in the UK over 19 years. Clin Microbiol Infect 13(1):78–85. https://doi.org/10.1111/j.1469-0691.2006.01558.x
Hatch TP (1975) Competition between Chlamydia psittaci and L cells for host isoleucine pools: a limiting factor in chlamydial multiplication. Infect Immun 12(1):211–220
Hatch TP, Allan I, Pearce JH (1984) Structural and polypeptide differences between envelopes of infective and reproductive life cycle forms of Chlamydia spp. J Bacteriol 157(1):13–20
Havell EA, Moldawer LL, Helfgott D, Kilian PL, Sehgal PB (1992) Type I IL-1 receptor blockade exacerbates murine listeriosis. J Immunol 148(5):1486–1492
Hempstead AD, Isberg RR (2015) Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response. Proc Natl Acad Sci USA 112(49):E6790–E6797. https://doi.org/10.1073/pnas.1508716112
Hill J, Samuel JE (2011) Coxiella burnetii acid phosphatase inhibits the release of reactive oxygen intermediates in polymorphonuclear leukocytes. Infect Immun 79(1):414–420. https://doi.org/10.1128/IAI.01011-10
Hirsch E, Irikura VM, Paul SM, Hirsh D (1996) Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc Natl Acad Sci USA 93(20):11008–11013
Hovel-Miner G, Faucher SP, Charpentier X, Shuman HA (2010) ArgR-regulated genes are derepressed in the Legionella-containing vacuole. J Bacteriol 192(17):4504–4516. https://doi.org/10.1128/JB.00465-10
Howe D, Heinzen RA (2006) Coxiella burnetii inhabits a cholesterol-rich vacuole and influences cellular cholesterol metabolism. Cell Microbiol 8(3):496–507. https://doi.org/10.1111/j.1462-5822.2005.00641.x
Howe D, Mallavia LP (1999) Coxiella burnetii infection increases transferrin receptors on J774A. 1 cells. Infect Immun 67(7):3236–3241
Hubber A, Roy CR (2010) Modulation of host cell function by Legionella pneumophila type IV effectors. Annu Rev Cell Dev Biol 26:261–283. https://doi.org/10.1146/annurev-cellbio-100109-104034
Ip WKE, Hoshi N, Shouval DS, Snapper S, Medzhitov R (2017) Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science 356(6337):513–519. https://doi.org/10.1126/science.aal3535
Jennings E, Thurston TLM, Holden DW (2017) Salmonella SPI-2 Type III secretion system effectors: molecular mechanisms and physiological consequences. Cell Host Microbe 22(2):217–231. https://doi.org/10.1016/j.chom.2017.07.009
Jo EK, Yuk JM, Shin DM, Sasakawa C (2013) Roles of autophagy in elimination of intracellular bacterial pathogens. Front Immunol 4:97. https://doi.org/10.3389/fimmu.2013.00097
Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA, Pei L, Hogenesch J, O’Connell RM, Cheng G, Saez E, Miller JF, Tontonoz P (2004) LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119(2):299–309. https://doi.org/10.1016/j.cell.2004.09.032
Jouanguy E, Doffinger R, Dupuis S, Pallier A, Altare F, Casanova JL (1999) IL-12 and IFN-gamma in host defense against mycobacteria and salmonella in mice and men. Curr Opin Immunol 11(3):346–351
Kading N, Szaszak M, Rupp J (2014) Imaging of Chlamydia and host cell metabolism. Future Microbiol 9(4):509–521. https://doi.org/10.2217/fmb.14.13
Kalman S, Mitchell W, Marathe R, Lammel C, Fan J, Hyman RW, Olinger L, Grimwood J, Davis RW, Stephens RS (1999) Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat Genet 21(4):385–389. https://doi.org/10.1038/7716
Kand’ar R, Zakova P, Muzakova V (2006) Monitoring of antioxidant properties of uric acid in humans for a consideration measuring of levels of allantoin in plasma by liquid chromatography. Clin Chim Acta 365(1–2):249–256. https://doi.org/10.1016/j.cca.2005.09.002
Kelly B, O’Neill LA (2015) Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res 25(7):771–784. https://doi.org/10.1038/cr.2015.68
Kim MJ, Wainwright HC, Locketz M, Bekker LG, Walther GB, Dittrich C, Visser A, Wang W, Hsu FF, Wiehart U, Tsenova L, Kaplan G, Russell DG (2010) Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism. EMBO Mol Med 2(7):258–274. https://doi.org/10.1002/emmm.201000079
Kim YK, Shin JS, Nahm MH (2016) NOD-like receptors in infection, immunity, and diseases. Yonsei Med J 57(1):5–14. https://doi.org/10.3349/ymj.2016.57.1.5
Kohler LJ, Roy CR (2015) Biogenesis of the lysosome-derived vacuole containing Coxiella burnetii. Microbes Infect 17(11–12):766–771. https://doi.org/10.1016/j.micinf.2015.08.006
Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, Cross JR, Jung E, Thompson CB, Jones RG, Pearce EJ (2010) Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 115(23):4742–4749. https://doi.org/10.1182/blood-2009-10-249540
Kuehl CJ, Dragoi AM, Talman A, Agaisse H (2015) Bacterial spread from cell to cell: beyond actin-based motility. Trends Microbiol 23(9):558–566. https://doi.org/10.1016/j.tim.2015.04.010
Kumar H, Kawai T, Akira S (2011) Pathogen recognition by the innate immune system. Int Rev Immunol 30(1):16–34. https://doi.org/10.3109/08830185.2010.529976
Lecuit M, Sonnenburg JL, Cossart P, Gordon JI (2007) Functional genomic studies of the intestinal response to a foodborne enteropathogen in a humanized gnotobiotic mouse model. J Biol Chem 282(20):15065–15072. https://doi.org/10.1074/jbc.M610926200
Leistikow RL, Morton RA, Bartek IL, Frimpong I, Wagner K, Voskuil MI (2010) The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy. J Bacteriol 192(6):1662–1670. https://doi.org/10.1128/JB.00926-09
Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469(7330):323–335. https://doi.org/10.1038/nature09782
Liao D, Fan Q, Bao L (2013) The role of superoxide dismutase in the survival of Mycobacterium tuberculosis in macrophages. Jpn J Infect Dis 66(6):480–488
Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 41(3):211–218. https://doi.org/10.1016/j.tibs.2015.12.001
Lin Z, Zhang YG, Xia Y, Xu X, Jiao X, Sun J (2016) Salmonella enteritidis effector AvrA stabilizes intestinal tight junctions via the JNK pathway. J Biol Chem 291(52):26837–26849. https://doi.org/10.1074/jbc.M116.757393
Liu X, Lu R, Xia Y, Sun J (2010) Global analysis of the eukaryotic pathways and networks regulated by Salmonella typhimurium in mouse intestinal infection in vivo. BMC Genomics 11:722. https://doi.org/10.1186/1471-2164-11-722
Lopez CA, Winter SE, Rivera-Chavez F, Xavier MN, Poon V, Nuccio SP, Tsolis RM, Baumler AJ (2012) Phage-mediated acquisition of a type III secreted effector protein boosts growth of salmonella by nitrate respiration. MBio 3(3). https://doi.org/10.1128/mBio.00143-12
Lutay N, Hakansson G, Alaridah N, Hallgren O, Westergren-Thorsson G, Godaly G (2014) Mycobacteria bypass mucosal NF-kB signalling to induce an epithelial anti-inflammatory IL-22 and IL-10 response. PLoS One 9(1):e86466. https://doi.org/10.1371/journal.pone.0086466
Macallan DC, McNurlan MA, Kurpad AV, de Souza G, Shetty PS, Calder AG, Griffin GE (1998) Whole body protein metabolism in human pulmonary tuberculosis and undernutrition: evidence for anabolic block in tuberculosis. Clin Sci (Lond) 94(3):321–331
Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, Rathmell JC (2014) The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 20(1):61–72. https://doi.org/10.1016/j.cmet.2014.05.004
Malhotra M, Sood S, Mukherjee A, Muralidhar S, Bala M (2013) Genital Chlamydia trachomatis: an update. Indian J Med Res 138(3):303–316
Manca C, Paul S, Barry CE 3rd, Freedman VH, Kaplan G (1999) Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro. Infect Immun 67(1):74–79
Mannonen L, Markkula E, Puolakkainen M (2011) Analysis of Chlamydia pneumoniae infection in mononuclear cells by reverse transcription-PCR targeted to chlamydial gene transcripts. Med Microbiol Immunol 200(3):143–154. https://doi.org/10.1007/s00430-011-0184-3
Mansell A, Braun L, Cossart P, O’Neill LA (2000) A novel function of InIB from Listeria monocytogenes: activation of NF-kappaB in J774 macrophages. Cell Microbiol 2(2):127–136
Manske C, Hilbi H (2014) Metabolism of the vacuolar pathogen Legionella and implications for virulence. Front Cell Infect Microbiol 4:125. https://doi.org/10.3389/fcimb.2014.00125
Mantegazza AR, Magalhaes JG, Amigorena S, Marks MS (2013) Presentation of phagocytosed antigens by MHC class I and II. Traffic 14(2):135–152. https://doi.org/10.1111/tra.12026
Marrero J, Rhee KY, Schnappinger D, Pethe K, Ehrt S (2010) Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection. Proc Natl Acad Sci USA 107(21):9819–9824. https://doi.org/10.1073/pnas.1000715107
Masoud GN, Li W (2015) HIF-1alpha pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B 5(5):378–389. https://doi.org/10.1016/j.apsb.2015.05.007
Matsunaga K, Klein TW, Newton C, Friedman H, Yamamoto Y (2001) Legionella pneumophila suppresses interleukin-12 production by macrophages. Infect Immun 69(3):1929–1933. https://doi.org/10.1128/IAI.69.3.1929-1933.2001
Meylan E, Tschopp J, Karin M (2006) Intracellular pattern recognition receptors in the host response. Nature 442(7098):39–44. https://doi.org/10.1038/nature04946
Michalek RD, Rathmell JC (2010) The metabolic life and times of a T-cell. Immunol Rev 236:190–202. https://doi.org/10.1111/j.1600-065X.2010.00911.x
Minton K (2017) Immune regulation: IL-10 targets macrophage metabolism. Nat Rev Immunol 17(6):345. https://doi.org/10.1038/nri.2017.57
Mishra BB, Rathinam VA, Martens GW, Martinot AJ, Kornfeld H, Fitzgerald KA, Sassetti CM (2013) Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1beta. Nat Immunol 14(1):52–60. https://doi.org/10.1038/ni.2474
Mishra BB, Lovewell RR, Olive AJ, Zhang G, Wang W, Eugenin E, Smith CM, Phuah JY, Long JE, Dubuke ML, Palace SG, Goguen JD, Baker RE, Nambi S, Mishra R, Booty MG, Baer CE, Shaffer SA, Dartois V, McCormick BA, Chen X, Sassetti CM (2017) Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat Microbiol 2:17072. https://doi.org/10.1038/nmicrobiol.2017.72
Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132. https://doi.org/10.1146/annurev-cellbio-092910-154005
Moffatt JH, Newton P, Newton HJ (2015) Coxiella burnetii: turning hostility into a home. Cell Microbiol 17(5):621–631. https://doi.org/10.1111/cmi.12432
Mulye M, Samanta D, Winfree S, Heinzen RA, Gilk SD (2017) Elevated cholesterol in the Coxiella burnetii intracellular niche is bacteriolytic. MBio 8(1). https://doi.org/10.1128/mBio.02313-16
Munn DH, Mellor AL (2013) Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 34(3):137–143. https://doi.org/10.1016/j.it.2012.10.001
Munoz-Elias EJ, McKinney JD (2006) Carbon metabolism of intracellular bacteria. Cell Microbiol 8(1):10–22. https://doi.org/10.1111/j.1462-5822.2005.00648.x
Nathan C, Shiloh MU (2000) Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci USA 97(16):8841–8848
Natividad A, Freeman TC, Jeffries D, Burton MJ, Mabey DC, Bailey RL, Holland MJ (2010) Human conjunctival transcriptome analysis reveals the prominence of innate defense in Chlamydia trachomatis infection. Infect Immun 78(11):4895–4911. https://doi.org/10.1128/IAI.00844-10
Ng VH, Cox JS, Sousa AO, MacMicking JD, McKinney JD (2004) Role of KatG catalase-peroxidase in mycobacterial pathogenesis: countering the phagocyte oxidative burst. Mol Microbiol 52(5):1291–1302. https://doi.org/10.1111/j.1365-2958.2004.04078.x
Nguyen GT, Green ER, Mecsas J (2017) Neutrophils to the ROScue: mechanisms of NADPH oxidase activation and bacterial resistance. Front Cell Infect Microbiol 7:373. https://doi.org/10.3389/fcimb.2017.00373
Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S (2012) Host-gut microbiota metabolic interactions. Science 336(6086):1262–1267. https://doi.org/10.1126/science.1223813
Ninio S, Roy CR (2007) Effector proteins translocated by Legionella pneumophila: strength in numbers. Trends Microbiol 15(8):372–380. https://doi.org/10.1016/j.tim.2007.06.006
O’Neill LA (2015) A broken krebs cycle in macrophages. Immunity 42(3):393–394. https://doi.org/10.1016/j.immuni.2015.02.017
O’Neill LA, Kishton RJ, Rathmell J (2016) A guide to immunometabolism for immunologists. Nat Rev Immunol 16(9):553–565. https://doi.org/10.1038/nri.2016.70
Odegaard JI, Chawla A (2011) Alternative macrophage activation and metabolism. Annu Rev Pathol 6:275–297. https://doi.org/10.1146/annurev-pathol-011110-130138
Olive AJ, Sassetti CM (2016) Metabolic crosstalk between host and pathogen: sensing, adapting and competing. Nat Rev Microbiol 14(4):221–234. https://doi.org/10.1038/nrmicro.2016.12
Omsland A, Sager J, Nair V, Sturdevant DE, Hackstadt T (2012) Developmental stage-specific metabolic and transcriptional activity of Chlamydia trachomatis in an axenic medium. Proc Natl Acad Sci USA 109(48):19781–19785. https://doi.org/10.1073/pnas.1212831109
Ouellette SP, Dorsey FC, Moshiach S, Cleveland JL, Carabeo RA (2011) Chlamydia species-dependent differences in the growth requirement for lysosomes. PLoS One 6(3):e16783. https://doi.org/10.1371/journal.pone.0016783
Pareja ME, Colombo MI (2013) Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms. Front Cell Infect Microbiol 3:54. https://doi.org/10.3389/fcimb.2013.00054
Pearce EL, Pearce EJ (2013) Metabolic pathways in immune cell activation and quiescence. Immunity 38(4):633–643. https://doi.org/10.1016/j.immuni.2013.04.005
Pearce EL, Poffenberger MC, Chang CH, Jones RG (2013) Fueling immunity: insights into metabolism and lymphocyte function. Science 342(6155):1242454. https://doi.org/10.1126/science.1242454
Peleg AY, Tampakakis E, Fuchs BB, Eliopoulos GM, Moellering RC Jr, Mylonakis E (2008) Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. Proc Natl Acad Sci USA 105(38):14585–14590. https://doi.org/10.1073/pnas.0805048105
Peng M, Yin N, Chhangawala S, Xu K, Leslie CS, Li MO (2016) Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science 354(6311):481–484. https://doi.org/10.1126/science.aaf6284
Peyron P, Vaubourgeix J, Poquet Y, Levillain F, Botanch C, Bardou F, Daffe M, Emile JF, Marchou B, Cardona PJ, de Chastellier C, Altare F (2008) Foamy macrophages from tuberculous patients' granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog 4(11):e1000204. https://doi.org/10.1371/journal.ppat.1000204
Pikuleva IA (2006) Cytochrome P450s and cholesterol homeostasis. Pharmacol Ther 112(3):761–773. https://doi.org/10.1016/j.pharmthera.2006.05.014
Plain KM, de Silva K, Earl J, Begg DJ, Purdie AC, Whittington RJ (2011) Indoleamine 2,3-dioxygenase, tryptophan catabolism, and Mycobacterium avium subsp. paratuberculosis: a model for chronic mycobacterial infections. Infect Immun 79(9):3821–3832. https://doi.org/10.1128/IAI.05204-11
Portnoy DA, Auerbuch V, Glomski IJ (2002) The cell biology of Listeria monocytogenes infection: the intersection of bacterial pathogenesis and cell-mediated immunity. J Cell Biol 158(3):409–414. https://doi.org/10.1083/jcb.200205009
Price CT, Al-Quadan T, Santic M, Rosenshine I, Abu Kwaik Y (2011) Host proteasomal degradation generates amino acids essential for intracellular bacterial growth. Science 334(6062):1553–1557. https://doi.org/10.1126/science.1212868
Price JD, Simpfendorfer KR, Mantena RR, Holden J, Heath WR, van Rooijen N, Strugnell RA, Wijburg OL (2007) Gamma interferon-independent effects of interleukin-12 on immunity to Salmonella enterica serovar Typhimurium. Infect Immun 75(12):5753–5762. https://doi.org/10.1128/IAI.00971-07
Ragno S, Romano M, Howell S, Pappin DJ, Jenner PJ, Colston MJ (2001) Changes in gene expression in macrophages infected with Mycobacterium tuberculosis: a combined transcriptomic and proteomic approach. Immunology 104(1):99–108
Ramirez-Alejo N, Santos-Argumedo L (2014) Innate defects of the IL-12/IFN-gamma axis in susceptibility to infections by mycobacteria and salmonella. J Interferon Cytokine Res 34(5):307–317. https://doi.org/10.1089/jir.2013.0050
Rao PK, Li Q (2009) Protein turnover in mycobacterial proteomics. Molecules 14(9):3237–3258. https://doi.org/10.3390/molecules14093237
Ren Q, Robertson SJ, Howe D, Barrows LF, Heinzen RA (2003) Comparative DNA microarray analysis of host cell transcriptional responses to infection by Coxiella burnetii or Chlamydia trachomatis. Ann N Y Acad Sci 990:701–713
Ribet D, Cossart P (2015) How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect 17(3):173–183. https://doi.org/10.1016/j.micinf.2015.01.004
Robertson DK, Gu L, Rowe RK, Beatty WL (2009) Inclusion biogenesis and reactivation of persistent Chlamydia trachomatis requires host cell sphingolipid biosynthesis. PLoS Pathog 5(11):e1000664. https://doi.org/10.1371/journal.ppat.1000664
Rosklint T, Ohlsson BG, Wiklund O, Noren K, Hulten LM (2002) Oxysterols induce interleukin-1beta production in human macrophages. Eur J Clin Invest 32(1):35–42
Santos RL, Raffatellu M, Bevins CL, Adams LG, Tukel C, Tsolis RM, Baumler AJ (2009) Life in the inflamed intestine, Salmonella style. Trends Microbiol 17(11):498–506. https://doi.org/10.1016/j.tim.2009.08.008
Scanu T, Spaapen RM, Bakker JM, Pratap CB, Wu LE, Hofland I, Broeks A, Shukla VK, Kumar M, Janssen H, Song JY, Neefjes-Borst EA, te Riele H, Holden DW, Nath G, Neefjes J (2015) Salmonella manipulation of host signaling pathways provokes cellular transformation associated with Gallbladder carcinoma. Cell Host Microbe 17(6):763–774. https://doi.org/10.1016/j.chom.2015.05.002
Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E (2004) The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 64(7):2627–2633
Scidmore MA, Fischer ER, Hackstadt T (1996) Sphingolipids and glycoproteins are differentially trafficked to the Chlamydia trachomatis inclusion. J Cell Biol 134(2):363–374
Shi L, Jung YJ, Tyagi S, Gennaro ML, North RJ (2003) Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium tuberculosis transcription pattern characteristic of nonreplicating persistence. Proc Natl Acad Sci USA 100(1):241–246. https://doi.org/10.1073/pnas.0136863100
Shi L, Salamon H, Eugenin EA, Pine R, Cooper A, Gennaro ML (2015) Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. Sci Rep 5:18176. https://doi.org/10.1038/srep18176
Shiloh MU, Manzanillo P, Cox JS (2008) Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection. Cell Host Microbe 3(5):323–330. https://doi.org/10.1016/j.chom.2008.03.007
Shin JH, Yang JY, Jeon BY, Yoon YJ, Cho SN, Kang YH, Ryu DH, Hwang GS (2011) (1)H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis. J Proteome Res 10(5):2238–2247. https://doi.org/10.1021/pr101054m
Siegl C, Prusty BK, Karunakaran K, Wischhusen J, Rudel T (2014) Tumor suppressor p53 alters host cell metabolism to limit Chlamydia trachomatis infection. Cell Rep 9(3):918–929. https://doi.org/10.1016/j.celrep.2014.10.004
Siemsen DW, Kirpotina LN, Jutila MA, Quinn MT (2009) Inhibition of the human neutrophil NADPH oxidase by Coxiella burnetii. Microbes Infect 11(6-7):671–679. https://doi.org/10.1016/j.micinf.2009.04.005
Singh V, Jamwal S, Jain R, Verma P, Gokhale R, Rao KV (2012) Mycobacterium tuberculosis-driven targeted recalibration of macrophage lipid homeostasis promotes the foamy phenotype. Cell Host Microbe 12(5):669–681. https://doi.org/10.1016/j.chom.2012.09.012
Singh V, Kaur C, Chaudhary VK, Rao KV, Chatterjee S (2015) M. tuberculosis secretory protein ESAT-6 induces metabolic flux perturbations to drive foamy macrophage differentiation. Sci Rep 5:12906. https://doi.org/10.1038/srep12906
Sinnis P, Ernst JD (2008) CO-opting the host HO-1 pathway in tuberculosis and malaria. Cell Host Microbe 3(5):277–279. https://doi.org/10.1016/j.chom.2008.04.009
Somashekar BS, Amin AG, Rithner CD, Troudt J, Basaraba R, Izzo A, Crick DC, Chatterjee D (2011) Metabolic profiling of lung granuloma in Mycobacterium tuberculosis infected guinea pigs: ex vivo 1H magic angle spinning NMR studies. J Proteome Res 10(9):4186–4195. https://doi.org/10.1021/pr2003352
Stratton CW, Sriram S (2003) Association of Chlamydia pneumoniae with central nervous system disease. Microbes Infect 5(13):1249–1253
Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ, O'Neill LA (2013) Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature 496(7444):238–242. https://doi.org/10.1038/nature11986
Tas SW, Vervoordeldonk MJ, Hajji N, Schuitemaker JH, van der Sluijs KF, May MJ, Ghosh S, Kapsenberg ML, Tak PP, de Jong EC (2007) Noncanonical NF-kappaB signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation. Blood 110(5):1540–1549. https://doi.org/10.1182/blood-2006-11-056010
Thiennimitr P, Winter SE, Winter MG, Xavier MN, Tolstikov V, Huseby DL, Sterzenbach T, Tsolis RM, Roth JR, Baumler AJ (2011) Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota. Proc Natl Acad Sci USA 108(42):17480–17485. https://doi.org/10.1073/pnas.1107857108
Tipples G, McClarty G (1993) The obligate intracellular bacterium Chlamydia trachomatis is auxotrophic for three of the four ribonucleoside triphosphates. Mol Microbiol 8(6):1105–1114
Uchiya K, Nikai T (2004) Salmonella enterica serovar Typhimurium infection induces cyclooxygenase 2 expression in macrophages: involvement of Salmonella pathogenicity island 2. Infect Immun 72(12):6860–6869. https://doi.org/10.1128/IAI.72.12.6860-6869.2004
van der Windt GJ, Pearce EL (2012) Metabolic switching and fuel choice during T-cell differentiation and memory development. Immunol Rev 249(1):27–42. https://doi.org/10.1111/j.1600-065X.2012.01150.x
van Ooij C, Kalman L, van I, Nishijima M, Hanada K, Mostov K, Engel JN (2000) Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis. Cell Microbiol 2(6):627–637
van Schaik EJ, Chen C, Mertens K, Weber MM, Samuel JE (2013) Molecular pathogenesis of the obligate intracellular bacterium Coxiella burnetii. Nat Rev Microbiol 11(8):561–573. https://doi.org/10.1038/nrmicro3049
Vazquez-Boland JA, Kuhn M, Berche P, Chakraborty T, Dominguez-Bernal G, Goebel W, Gonzalez-Zorn B, Wehland J, Kreft J (2001) Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 14(3):584–640. https://doi.org/10.1128/CMR.14.3.584-640.2001
Verreck FA, de Boer T, Langenberg DM, Hoeve MA, Kramer M, Vaisberg E, Kastelein R, Kolk A, de Waal-Malefyt R, Ottenhoff TH (2004) Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc Natl Acad Sci USA 101(13):4560–4565. https://doi.org/10.1073/pnas.0400983101
Vonaesch P, Sellin ME, Cardini S, Singh V, Barthel M, Hardt WD (2014) The Salmonella Typhimurium effector protein SopE transiently localizes to the early SCV and contributes to intracellular replication. Cell Microbiol 16(12):1723–1735. https://doi.org/10.1111/cmi.12333
Vromman F, Laverriere M, Perrinet S, Dufour A, Subtil A (2014) Quantitative monitoring of the Chlamydia trachomatis developmental cycle using GFP-expressing bacteria, microscopy and flow cytometry. PLoS One 9(6):e99197. https://doi.org/10.1371/journal.pone.0099197
Wagner RD, Steinberg H, Brown JF, Czuprynski CJ (1994) Recombinant interleukin-12 enhances resistance of mice to Listeria monocytogenes infection. Microb Pathog 17(3):175–186
Wahl DR, Byersdorfer CA, Ferrara JL, Opipari AW Jr, Glick GD (2012) Distinct metabolic programs in activated T cells: opportunities for selective immunomodulation. Immunol Rev 249(1):104–115. https://doi.org/10.1111/j.1600-065X.2012.01148.x
Way SS, Havenar-Daughton C, Kolumam GA, Orgun NN, Murali-Krishna K (2007) IL-12 and type-I IFN synergize for IFN-gamma production by CD4 T cells, whereas neither are required for IFN-gamma production by CD8 T cells after Listeria monocytogenes infection. J Immunol 178(7):4498–4505
Wieland H, Ullrich S, Lang F, Neumeister B (2005) Intracellular multiplication of Legionella pneumophila depends on host cell amino acid transporter SLC1A5. Mol Microbiol 55(5):1528–1537. https://doi.org/10.1111/j.1365-2958.2005.04490.x
Wylie JL, Hatch GM, McClarty G (1997) Host cell phospholipids are trafficked to and then modified by Chlamydia trachomatis. J Bacteriol 179(23):7233–7242
Yamada H, Mizuno S, Reza-Gholizadeh M, Sugawara I (2001) Relative importance of NF-kappaB p50 in mycobacterial infection. Infect Immun 69(11):7100–7105. https://doi.org/10.1128/IAI.69.11.7100-7105.2001
Zaika AI, Wei J, Noto JM, Peek RM (2015) Microbial regulation of p53 tumor suppressor. PLoS Pathog 11(9):e1005099. https://doi.org/10.1371/journal.ppat.1005099
Zhang YJ, Reddy MC, Ioerger TR, Rothchild AC, Dartois V, Schuster BM, Trauner A, Wallis D, Galaviz S, Huttenhower C, Sacchettini JC, Behar SM, Rubin EJ (2013) Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing. Cell 155(6):1296–1308. https://doi.org/10.1016/j.cell.2013.10.045
Zou T, Garifulin O, Berland R, Boyartchuk VL (2011) Listeria monocytogenes infection induces prosurvival metabolic signaling in macrophages. Infect Immun 79(4):1526–1535. https://doi.org/10.1128/IAI.01195-10
Acknowledgments
Our work is funded by the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and the Fundação para a Ciência e Tecnologia (FCT) through the FCT investigator grant IF/01390/2014 to E.T. and the PhD fellowship SFRH/BD/120371/2016 to A.M.B.
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Ferreira, C.M., Barbosa, A.M., Pereira, I.M., Torrado, E. (2018). Metabolic Host Response to Intracellular Infections. In: Silvestre, R., Torrado, E. (eds) Metabolic Interaction in Infection. Experientia Supplementum, vol 109. Springer, Cham. https://doi.org/10.1007/978-3-319-74932-7_8
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