Advertisement

Regulation of Innate Inflammatory Responses

  • Walter Gottlieb Land
Chapter

Abstract

This chapter addressed one of the most important issues of inflammatory innate immune effector responses: mechanisms of their regulation aimed at avoiding auto-destructive “suicidal” pathologies caused by uncontrolled exaggerated DAMP-induced inflammatory pathways. From the various evolutionarily developed regulatory mechanisms described in the literature, here, three essential regulatory mechanisms are briefly highlighted: epigenetic reprogramming, post-translational modifications, and metabolic changes. Regulating epigenetic changes can be categorized into several major biochemical mechanisms, including changes in (1) DNA methylation; (2) covalent histone post-translational modifications such as histone acetylation, methylation, phosphorylation, and ubiquitination; and (3) RNA-based mechanisms as mediated by small and long non-coding RNAs. Such chromatin modifiers were shown to execute coordinated actions to convert extracellular stimuli into the complex gene expression patterns during innate inflammatory responses. As a striking example of epigenetic regulation, the phenomenon of “trained immunity” is briefly touched reflecting the fact that the innate immune system—like the adaptive immune system—possesses a memory as well. In addition, evidence is presented for a role of post-translational modifications such as phosphorylation, methylation, or acetylation in influencing PRM-dependent inflammatory responses via targeting of innate sensors and downstream signalling molecules, including receptors, adaptors, enzymes, and transcriptional factors. Finally, in this chapter, some remarks are made regarding profound changes in intracellular metabolic pathways in innate immune cells such as dendritic cells and macrophages that alter their function when getting activated to execute effector responses. As a typical metabolic modification, the shift from mitochondrial oxidative phosphorylation in resting innate immune cells to aerobic glycolysis in activated cells is particularly mentioned.

References

  1. 1.
    Liu J, Qian C, Cao X. Post-translational modification control of innate immunity. Immunity. 2016;45:15–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27438764 CrossRefGoogle Scholar
  2. 2.
    Smale ST, Tarakhovsky A, Natoli G. Chromatin contributions to the regulation of innate immunity. Annu Rev Immunol. 2014;32:489–511. Available from: http://www.annualreviews.org/doi/10.1146/annurev-immunol-031210-101303 CrossRefGoogle Scholar
  3. 3.
    Álvarez-Errico D, Vento-Tormo R, Sieweke M, Ballestar E. Epigenetic control of myeloid cell differentiation, identity and function. Nat Rev Immunol. 2015;15:7–17. Available from: http://www.nature.com/doifinder/10.1038/nri3777 CrossRefGoogle Scholar
  4. 4.
    Waterland RA. Epigenetic mechanisms and gastrointestinal development. J Pediatr. 2006;149:S137–42. Available from: http://linkinghub.elsevier.com/retrieve/pii/S002234760600624X CrossRefGoogle Scholar
  5. 5.
    Schreiber J, Jenner RG, Murray HL, Gerber GK, Gifford DK, Young RA. Coordinated binding of NF-kappaB family members in the response of human cells to lipopolysaccharide. Proc Natl Acad Sci U S A. 2006;103:5899–904. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.0510996103 CrossRefPubMedCentralGoogle Scholar
  6. 6.
    Gibney ER, Nolan CM. Epigenetics and gene expression. Heredity (Edinb). 2010;105:4–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20461105 CrossRefGoogle Scholar
  7. 7.
    Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, et al. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518:317–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25693563 CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Rothbart SB, Strahl BD. Interpreting the language of histone and DNA modifications. Biochim Biophys Acta. 2014;1839:627–43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24631868 CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Wei J-W, Huang K, Yang C, Kang C-S. Non-coding RNAs as regulators in epigenetics (Review). Oncol Rep. 2016;37:3–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27841002 CrossRefGoogle Scholar
  10. 10.
    Moosavi A, Motevalizadeh Ardekani A. Role of epigenetics in biology and human diseases. Iran Biomed J. 2016;20:246–58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27377127 PubMedPubMedCentralGoogle Scholar
  11. 11.
    Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet. 2016;17:487–500. Available from: http://www.nature.com/doifinder/10.1038/nrg.2016.59 CrossRefGoogle Scholar
  12. 12.
    Torres IO, Fujimori DG. Functional coupling between writers, erasers and readers of histone and DNA methylation. Curr Opin Struct Biol. 2015;35:68–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26496625 CrossRefPubMedCentralGoogle Scholar
  13. 13.
    Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009;23:781–3. Available from: http://genesdev.cshlp.org/cgi/doi/10.1101/gad.1787609 CrossRefPubMedCentralGoogle Scholar
  14. 14.
    Kreuz S, Fischle W. Oxidative stress signaling to chromatin in health and disease. Epigenomics. 2016;8:843–62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27319358 CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Heinz S, Romanoski CE, Benner C, Glass CK. The selection and function of cell type-specific enhancers. Nat Rev Mol Cell Biol. 2015;16:144–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25650801 CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Hoeksema MA, de Winther MPJ. Epigenetic regulation of monocyte and macrophage function. Antioxid Redox Signal. 2016;25:758–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26983461 CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Ghisletti S, Natoli G. Deciphering cis-regulatory control in inflammatory cells. Philos Trans R Soc B Biol Sci. 2013;368:20120370. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23650641 CrossRefGoogle Scholar
  18. 18.
    Xu Y, Zhang S, Lin S, Guo Y, Deng W, Zhang Y, et al. WERAM: a database of writers, erasers and readers of histone acetylation and methylation in eukaryotes. Nucleic Acids Res. 2017;45:D264–70. Available from: https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw1011 PubMedGoogle Scholar
  19. 19.
    Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F, Venturini E, et al. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity. 2010;32:317–28. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1074761310000786 CrossRefGoogle Scholar
  20. 20.
    Busslinger M, Tarakhovsky A. Epigenetic control of immunity. Cold Spring Harb Perspect Biol. 2014;6:a019307. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24890513 CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Mehta S, Jeffrey KL. Beyond receptors and signaling: epigenetic factors in the regulation of innate immunity. Immunol Cell Biol. 2015;93:233–44. Available from: http://www.nature.com/doifinder/10.1038/icb.2014.101 CrossRefPubMedCentralGoogle Scholar
  22. 22.
    Hennessy C, McKernan DP. Epigenetics and innate immunity: the “unTolld” story. Immunol Cell Biol. 2016;94:631–9. Available from: http://www.nature.com/doifinder/10.1038/icb.2016.24 CrossRefGoogle Scholar
  23. 23.
    Cao X. Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat Rev Immunol. 2016;16:35–50. Available from: http://www.nature.com/doifinder/10.1038/nri.2015.8 CrossRefGoogle Scholar
  24. 24.
    Liu J, Cao X. Cellular and molecular regulation of innate inflammatory responses. Cell Mol Immunol. 2016;13:711–21. Available from: http://www.nature.com/doifinder/10.1038/cmi.2016.58 CrossRefPubMedCentralGoogle Scholar
  25. 25.
    Ramirez-Carrozzi VR, Braas D, Bhatt DM, Cheng CS, Hong C, Doty KR, et al. A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell. 2009;138:114–28. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0092867409004450 CrossRefPubMedCentralGoogle Scholar
  26. 26.
    Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung C-W, et al. Suppression of inflammation by a synthetic histone mimic. Nature. 2010;468:1119–23. Available from: http://www.nature.com/doifinder/10.1038/nature09589 CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Garber M, Yosef N, Goren A, Raychowdhury R, Thielke A, Guttman M, et al. A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals. Mol Cell. 2012;47:810–22. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1097276512006570 CrossRefGoogle Scholar
  28. 28.
    Zhang Y, Cao X. Long noncoding RNAs in innate immunity. Cell Mol Immunol. 2016;13:138–47. Available from: http://www.nature.com/doifinder/10.1038/cmi.2015.68 CrossRefGoogle Scholar
  29. 29.
    Nishitsuji H, Ujino S, Yoshio S, Sugiyama M, Mizokami M, Kanto T, et al. Long noncoding RNA #32 contributes to antiviral responses by controlling interferon-stimulated gene expression. Proc Natl Acad Sci U S A. 2016;113:10388–93. Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1525022113 CrossRefPubMedCentralGoogle Scholar
  30. 30.
    Li X, Zhang Q, Ding Y, Liu Y, Zhao D, Zhao K, et al. Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity. Nat Immunol. 2016;17:806–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27240213 CrossRefGoogle Scholar
  31. 31.
    Barish GD, Yu RT, Karunasiri M, Ocampo CB, Dixon J, Benner C, et al. Bcl-6 and NF-kappaB cistromes mediate opposing regulation of the innate immune response. Genes Dev. 2010;24:2760–5. Available from: http://genesdev.cshlp.org/cgi/doi/10.1101/gad.1998010 CrossRefPubMedCentralGoogle Scholar
  32. 32.
    Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–89. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1097276510003667 CrossRefPubMedCentralGoogle Scholar
  33. 33.
    Schliehe C, Flynn EK, Vilagos B, Richson U, Swaminathan S, Bosnjak B, et al. The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection. Nat Immunol. 2015;16:67–74. Available from: http://www.nature.com/doifinder/10.1038/ni.3046 CrossRefGoogle Scholar
  34. 34.
    Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22663078 CrossRefGoogle Scholar
  35. 35.
    Carpenter S, Aiello D, Atianand MK, Ricci EP, Gandhi P, Hall LL, et al. A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013;341:789–92. Available from: http://www.sciencemag.org/cgi/doi/10.1126/science.1240925 CrossRefPubMedCentralGoogle Scholar
  36. 36.
    Turner M, Galloway A, Vigorito E. Noncoding RNA and its associated proteins as regulatory elements of the immune system. Nat Immunol. 2014;15:484–91. Available from: http://www.nature.com/doifinder/10.1038/ni.2887 CrossRefGoogle Scholar
  37. 37.
    Atianand MK, Caffrey DR, Fitzgerald KA. Immunobiology of long noncoding RNAs. Annu Rev Immunol. 2017;35:177–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28125358 CrossRefGoogle Scholar
  38. 38.
    Hu G, Gong A-Y, Wang Y, Ma S, Chen X, Chen J, et al. LincRNA-Cox2 promotes late inflammatory gene transcription in macrophages through modulating SWI/SNF-mediated chromatin remodeling. J Immunol. 2016;196:2799–808. Available from: http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.1502146 CrossRefPubMedCentralGoogle Scholar
  39. 39.
    Ma S, Ming Z, Gong A-Y, Wang Y, Chen X, Hu G, et al. A long noncoding RNA, lincRNA-Tnfaip3, acts as a coregulator of NF-κB to modulate inflammatory gene transcription in mouse macrophages. FASEB J. 2017;31(3):1215–25. Available from: http://www.fasebj.org/cgi/doi/10.1096/fj.201601056R CrossRefGoogle Scholar
  40. 40.
    Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell. 2009;33:717–26. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1097276509000707 CrossRefPubMedCentralGoogle Scholar
  41. 41.
    Hirose T, Virnicchi G, Tanigawa A, Naganuma T, Li R, Kimura H, et al. NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol Biol Cell. 2014;25:169–83. Available from: http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E13-09-0558 CrossRefPubMedCentralGoogle Scholar
  42. 42.
    Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, et al. Long noncoding RNA NEAT1-dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 expression upon immune stimuli. Mol Cell. 2014;53:393–406. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1097276514000410 CrossRefGoogle Scholar
  43. 43.
    Netea MG, Quintin J, van der Meer JWM. Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011;9:355–61. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1931312811001284 CrossRefGoogle Scholar
  44. 44.
    Netea MG, Latz E, Mills KHG, O’Neill LAJ. Innate immune memory: a paradigm shift in understanding host defense. Nat Immunol. 2015;16:675–9. Available from: http://www.nature.com/doifinder/10.1038/ni.3178 CrossRefGoogle Scholar
  45. 45.
    Netea MG, Joosten LAB, Latz E, Mills KHG, Natoli G, Stunnenberg HG, et al. Trained immunity: a program of innate immune memory in health and disease. Science. 2016;352:aaf1098. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27102489 CrossRefPubMedCentralGoogle Scholar
  46. 46.
    Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, et al. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe. 2012;12:223–32. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1931312812002326 CrossRefGoogle Scholar
  47. 47.
    Crisan TO, Netea MG, Joosten LAB. Innate immune memory: implications for host responses to damage-associated molecular patterns. Eur J Immunol. 2016;46:817–8.  https://doi.org/10.1002/eji.201545497.CrossRefPubMedGoogle Scholar
  48. 48.
    Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis. 2011;204:245–52. Available from: https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jir240 CrossRefGoogle Scholar
  49. 49.
    Biering-Sørensen S, Aaby P, Napirna BM, Roth A, Ravn H, Rodrigues A, et al. Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guérin vaccination at first health center contact. Pediatr Infect Dis J. 2012;31:306–8. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00006454-201203000-00021 CrossRefGoogle Scholar
  50. 50.
    Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, et al. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature. 2007;447:326–9. Available from: http://www.nature.com/doifinder/10.1038/nature05762 CrossRefGoogle Scholar
  51. 51.
    Kleinnijenhuis J, Quintin J, Preijers F, Joosten LAB, Ifrim DC, Saeed S, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012;109:17537–42. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.1202870109 CrossRefPubMedCentralGoogle Scholar
  52. 52.
    Saeed S, Quintin J, Kerstens HHD, Rao NA, Aghajanirefah A, Matarese F, et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science. 2014;345:1251086. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25258085 CrossRefPubMedCentralGoogle Scholar
  53. 53.
    Fan H, Cook JA. Molecular mechanisms of endotoxin tolerance. J Endotoxin Res. 2004;10:71–84. Available from: http://www.ingentaselect.com/rpsv/cgi-bin/cgi?ini=xref&body=linker&reqdoi=10.1179/096805104225003997 CrossRefGoogle Scholar
  54. 54.
    Foster SL, Hargreaves DC, Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature. 2007;447:972–8. Available from: http://www.nature.com/doifinder/10.1038/nature05836 CrossRefGoogle Scholar
  55. 55.
    Ifrim DC, Quintin J, Joosten LAB, Jacobs C, Jansen T, Jacobs L, et al. Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clin Vaccine Immunol. 2014;21:534–45. Available from: http://cvi.asm.org/cgi/doi/10.1128/CVI.00688-13 CrossRefPubMedCentralGoogle Scholar
  56. 56.
    Burgess SL, Buonomo E, Carey M, Cowardin C, Naylor C, Noor Z, et al. Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis. MBio. 2014;5:e01817. Available from: http://mbio.asm.org/lookup/doi/10.1128/mBio.01817-14 CrossRefPubMedCentralGoogle Scholar
  57. 57.
    Cheng S-C, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, et al. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014;345:1250684. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25258083 CrossRefPubMedCentralGoogle Scholar
  58. 58.
    Lamb DJ, Eales LJ, Ferns GA. Immunization with bacillus Calmette-Guerin vaccine increases aortic atherosclerosis in the cholesterol-fed rabbit. Atherosclerosis. 1999;143:105–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10208485 CrossRefGoogle Scholar
  59. 59.
    Land WG. The role of damage-associated molecular patterns (DAMPs) in human diseases: Part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine. Sultan Qaboos Univ Med J. 2015;15:e157–70. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26052447 PubMedPubMedCentralGoogle Scholar
  60. 60.
    Bekkering S, Quintin J, Joosten LAB, van der Meer JWM, Netea MG, Riksen NP. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler Thromb Vasc Biol. 2014;34:1731–8. Available from: http://atvb.ahajournals.org/cgi/doi/10.1161/ATVBAHA.114.303887 CrossRefGoogle Scholar
  61. 61.
    Crisan TO, Cleophas MCP, Oosting M, Lemmers H, Toenhake-Dijkstra H, Netea MG, et al. Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra. Ann Rheum Dis. 2016;75:755–62. Available from: http://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2014-206564 CrossRefGoogle Scholar
  62. 62.
    Valdés-Ferrer SI, Rosas-Ballina M, Olofsson PS, Lu B, Dancho ME, Li J, et al. High-mobility group box 1 mediates persistent splenocyte priming in sepsis survivors. Shock. 2013;40:492–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24089009 CrossRefPubMedCentralGoogle Scholar
  63. 63.
    Netea MG, van der Meer JWM. Trained immunity: an ancient way of remembering. Cell Host Microbe. 2017;21:297–300. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28279335 CrossRefGoogle Scholar
  64. 64.
    Rogers LD, Overall CM. Proteolytic post-translational modification of proteins: proteomic tools and methodology. Mol Cell Proteomics. 2013;12:3532–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23887885 CrossRefPubMedCentralGoogle Scholar
  65. 65.
    Salvesen GS, Dixit VM. Caspases: intracellular signaling by proteolysis. Cell. 1997;91:443–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9390553 CrossRefGoogle Scholar
  66. 66.
    Deribe YL, Pawson T, Dikic I. Post-translational modifications in signal integration. Nat Struct Mol Biol. 2010;17:666–72. Available from: http://www.nature.com/doifinder/10.1038/nsmb.1842 CrossRefGoogle Scholar
  67. 67.
    Mowen KA, David M. Unconventional post-translational modifications in immunological signaling. Nat Immunol. 2014;15:512–20. Available from: http://www.nature.com/doifinder/10.1038/ni.2873 CrossRefGoogle Scholar
  68. 68.
    Potempa J. Posttranslational modifications in Innate immunity. J Innate Immun. 2012;4:119–20. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22286943 CrossRefGoogle Scholar
  69. 69.
    Chiang C, Gack MU. Post-translational control of intracellular pathogen sensing pathways. Trends Immunol. 2017;38:39–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27863906 CrossRefGoogle Scholar
  70. 70.
    Wu J, Chen ZJ. Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol. 2014;32:461–88. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24655297 CrossRefGoogle Scholar
  71. 71.
    Seo GJ, Yang A, Tan B, Kim S, Liang Q, Choi Y, et al. Akt kinase-mediated checkpoint of cGAS DNA sensing pathway. Cell Rep. 2015;13:440–9. Available from: http://linkinghub.elsevier.com/retrieve/pii/S2211124715010189 CrossRefPubMedCentralGoogle Scholar
  72. 72.
    Shu H-B, Wang Y-Y. Adding to the STING. Immunity. 2014;41:871–3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25526298 CrossRefGoogle Scholar
  73. 73.
    Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, et al. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity. 2010;33:765–76. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1074761310003997 CrossRefGoogle Scholar
  74. 74.
    Zhang J, Hu M-M, Wang Y-Y, Shu H-B. TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination. J Biol Chem. 2012;287:28646–55. Available from: http://www.jbc.org/cgi/doi/10.1074/jbc.M112.362608 CrossRefPubMedCentralGoogle Scholar
  75. 75.
    Krawczyk CM, Holowka T, Sun J, Blagih J, Amiel E, DeBerardinis RJ, et al. Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood. 2010;115:4742–9. Available from: http://www.bloodjournal.org/cgi/doi/10.1182/blood-2009-10-249540 CrossRefPubMedCentralGoogle Scholar
  76. 76.
    McGettrick AF, O’Neill LAJ. How metabolism generates signals during innate immunity and inflammation. J Biol Chem. 2013;288:22893–8. Available from: http://www.jbc.org/lookup/doi/10.1074/jbc.R113.486464 CrossRefPubMedCentralGoogle Scholar
  77. 77.
    Everts B, Amiel E, Huang SC-C, Smith AM, Chang C-H, Lam WY, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation. Nat Immunol. 2014;15:323–32. Available from: http://www.nature.com/doifinder/10.1038/ni.2833 CrossRefPubMedCentralGoogle Scholar
  78. 78.
    Pearce EJ, Everts B. Dendritic cell metabolism. Nat Rev Immunol. 2015;15:18–29. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25534620 CrossRefPubMedCentralGoogle Scholar
  79. 79.
    O’Neill LAJ, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16:553–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27396447 CrossRefPubMedCentralGoogle Scholar
  80. 80.
    O’Neill L. Immunometabolism and the land of milk and honey. Nat Rev Immunol. 2017;17:217. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28287105 CrossRefGoogle Scholar
  81. 81.
    Langston PK, Shibata M, Horng T. Metabolism supports macrophage activation. Front Immunol. 2017;8:61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28197151 CrossRefPubMedCentralGoogle Scholar
  82. 82.
    Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013;496:238–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23535595 CrossRefPubMedCentralGoogle Scholar
  83. 83.
    Jha AK, Huang SC-C, Sergushichev A, Lampropoulou V, Ivanova Y, Loginicheva E, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity. 2015;42:419–30. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1074761315000801 CrossRefGoogle Scholar
  84. 84.
    Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19872213 CrossRefPubMedCentralGoogle Scholar
  85. 85.
    Xu J, Li J, Yu Z, Rao H, Wang S, Lan H. HMGB1 promotes HLF-1 proliferation and ECM production through activating HIF1-α-regulated aerobic glycolysis. Pulm Pharmacol Ther. 2017;45:136–41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28571757 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of StrasbourgMolecular ImmunoRheumatology, Laboratory of Excellence TransplantexStrasbourgFrance

Personalised recommendations