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Inflammasome Signaling and Bacterial Infections pp 183–197Cite as

Inflammasome Activation and Function During Infection with Mycobacterium Tuberculosis

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 397))

Abstract

Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis (Mtb) and represents one of the most relevant bacterial diseases worldwide. Recent advances have yielded new insights into the molecular basis of the immune response required for restriction of the pathogen and also highlighted determinants of immunopathology in TB. Several innate immune mediators including soluble proteins as well as lipid molecules participate in both processes, and their mechanisms of action during TB have been extensively studies over the past years. Among those mediators, inflammasomes are essential signaling platforms that execute crucial functions in several areas of immunology and beyond. This chapter aims to summarize what is known about the roles of the inflammasome during infection with Mtb from both in vitro studies as well as from in vivo work. A better understanding of the complex interactions between Mtb and the host immune system could reveal novel therapeutic approaches and improve current vaccination protocols in TB.

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References

  • Abdalla H, Srinivasan L, Shah S, Mayer-Barber KD, Sher A, Sutterwala FS, Briken V (2012) Mycobacterium tuberculosis infection of dendritic cells leads to partially caspase-1/11-independent IL-1beta and IL-18 secretion but not to pyroptosis. PLoS ONE 7:e40722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abdallah AM, Bestebroer J, Savage ND, de Punder K, van Zon M, Wilson L, Korbee CJ, van der Sar AM, Ottenhoff TH, van der Wel NN et al (2011) Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation. J Immunol 187:4744–4753

    Article  CAS  PubMed  Google Scholar 

  • Abel L, El-Baghdadi J, Bousfiha AA, Casanova JL, Schurr E (2014) Human genetics of tuberculosis: a long and winding road. Philos Trans R Soc Lond B Biol Sci 369:20130428

    Article  PubMed  PubMed Central  Google Scholar 

  • Ates LS, Houben EN, Bitter W (2016) Type VII secretion: a highly versatile secretion system. Microbiology spectrum 4

    Google Scholar 

  • Collins AC, Cai H, Li T, Franco LH, Li XD, Nair VR, Scharn CR, Stamm CE, Levine B, Chen ZJ et al (2015) Cyclic GMP-AMP synthase is an innate immune DNA sensor for Mycobacterium tuberculosis. Cell Host Microbe 17:820–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Court N, Vasseur V, Vacher R, Fremond C, Shebzukhov Y, Yeremeev VV, Maillet I, Nedospasov SA, Gordon S, Fallon PG et al (2010) Partial redundancy of the pattern recognition receptors, scavenger receptors, and C-type lectins for the long-term control of Mycobacterium tuberculosis infection. J Immunol 184:7057–7070

    Article  CAS  PubMed  Google Scholar 

  • de Jonge MI, Pehau-Arnaudet G, Fretz MM, Romain F, Bottai D, Brodin P, Honore N, Marchal G, Jiskoot W, England P et al (2007) ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP-10 under acidic conditions and exhibits membrane-lysing activity. J Bacteriol 189:6028–6034

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Paolo NC, Shafiani S, Day T, Papayannoupoulou T, Russell DW, Iwakura Y, Sherman D, Urdahl K, Shayakhmetov DM (2015) Interdependence between Interleukin-1 and tumor necrosis factor regulates TNF-dependent control of Mycobacterium tuberculosis infection. Immunity 43:1125–1136

    Article  PubMed  Google Scholar 

  • Divangahi M, Mostowy S, Coulombe F, Kozak R, Guillot L, Veyrier F, Kobayashi KS, Flavell RA, Gros P, Behr MA (2008) NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity. J Immunol 181:7157–7165

    Article  CAS  PubMed  Google Scholar 

  • Dorhoi A, Kaufmann SH (2014) Tumor necrosis factor alpha in mycobacterial infection. Semin Immunol 26:203–209

    Article  CAS  PubMed  Google Scholar 

  • Dorhoi A, Kaufmann SH (2015) Versatile myeloid cell subsets contribute to tuberculosis-associated inflammation. Eur J Immunol 45:2191–2202

    Article  CAS  PubMed  Google Scholar 

  • Dorhoi A, Desel C, Yeremeev V, Pradl L, Brinkmann V, Mollenkopf HJ, Hanke K, Gross O, Ruland J, Kaufmann SH (2010) The adaptor molecule CARD9 is essential for tuberculosis control. J Exp Med 207:777–792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorhoi A, Nouailles G, Jorg S, Hagens K, Heinemann E, Pradl L, Oberbeck-Muller D, Duque-Correa MA, Reece ST, Ruland J et al (2012) Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis. Eur J Immunol 42:374–384

    Article  CAS  PubMed  Google Scholar 

  • Dorhoi A, Iannaccone M, Farinacci M, Fae KC, Schreiber J, Moura-Alves P, Nouailles G, Mollenkopf HJ, Oberbeck-Muller D, Jorg S et al (2013) MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment. J Clin Investig 123:4836–4848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eklund D, Welin A, Andersson H, Verma D, Soderkvist P, Stendahl O, Sarndahl E, Lerm M (2014) Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis. J Infect Dis 209:749–753

    Article  CAS  PubMed  Google Scholar 

  • Ferwerda G, Girardin SE, Kullberg BJ, Le Bourhis L, de Jong DJ, Langenberg DM, van Crevel R, Adema GJ, Ottenhoff TH, Van der Meer JW et al (2005) NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog 1:279–285

    Article  CAS  PubMed  Google Scholar 

  • Fremond CM, Yeremeev V, Nicolle DM, Jacobs M, Quesniaux VF, Ryffel B (2004) Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. J Clin Investig 114:1790–1799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fremond CM, Togbe D, Doz E, Rose S, Vasseur V, Maillet I, Jacobs M, Ryffel B, Quesniaux VF (2007) IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J Immunol 179:1178–1189

    Article  CAS  PubMed  Google Scholar 

  • Gandotra S, Jang S, Murray PJ, Salgame P, Ehrt S (2007) Nucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis. Infect Immun 75:5127–5134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gringhuis SI, Kaptein TM, Wevers BA, Theelen B, van der Vlist M, Boekhout T, Geijtenbeek TB (2012) Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1beta via a noncanonical caspase-8 inflammasome. Nat Immunol 13:246–254

    Article  CAS  PubMed  Google Scholar 

  • Gross O, Thomas CJ, Guarda G, Tschopp J (2011) The inflammasome: an integrated view. Immunol Rev 243:136–151

    Article  CAS  PubMed  Google Scholar 

  • Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C, Forster I, Farlik M, Decker T, Du Pasquier RA, Romero P et al (2011) Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34:213–223

    Article  CAS  PubMed  Google Scholar 

  • Heitmann L, Schoenen H, Ehlers S, Lang R, Holscher C (2013) Mincle is not essential for controlling Mycobacterium tuberculosis infection. Immunobiology 218:506–516

    Article  CAS  PubMed  Google Scholar 

  • Holscher C, Reiling N, Schaible UE, Holscher A, Bathmann C, Korbel D, Lenz I, Sonntag T, Kroger S, Akira S et al (2008) Containment of aerogenic Mycobacterium tuberculosis infection in mice does not require MyD88 adaptor function for TLR2, -4 and -9. Eur J Immunol 38:680–694

    Article  PubMed  Google Scholar 

  • Houben D, Demangel C, van Ingen J, Perez J, Baldeon L, Abdallah AM, Caleechurn L, Bottai D, van Zon M, de Punder K et al (2012) ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria. Cell Microbiol 14:1287–1298

    Article  CAS  PubMed  Google Scholar 

  • Hsu T, Hingley-Wilson SM, Chen B, Chen M, Dai AZ, Morin PM, Marks CB, Padiyar J, Goulding C, Gingery M et al (2003) The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc Natl Acad Sci USA 100:12420–12425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jayaraman P, Sada-Ovalle I, Nishimura T, Anderson AC, Kuchroo VK, Remold HG, Behar SM (2013) IL-1beta promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. J Immunol 190:4196–4204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koo IC, Wang C, Raghavan S, Morisaki JH, Cox JS, Brown EJ (2008) ESX-1-dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection. Cell Microbiol 10:1866–1878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lowe DM, Redford PS, Wilkinson RJ, O’Garra A, Martineau AR (2012) Neutrophils in tuberculosis: friend or foe? Trends Immunol 33:14–25

    Article  CAS  PubMed  Google Scholar 

  • Majlessi L, Prados-Rosales R, Casadevall A, Brosch R (2015) Release of mycobacterial antigens. Immunol Rev 264:25–45

    Article  CAS  PubMed  Google Scholar 

  • Man SM, Kanneganti TD (2016) Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat Rev Immunol 16:7–21

    Article  CAS  PubMed  Google Scholar 

  • Manzanillo PS, Shiloh MU, Portnoy DA, Cox JS (2012) Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages. Cell Host Microbe 11:469–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Master SS, Rampini SK, Davis AS, Keller C, Ehlers S, Springer B, Timmins GS, Sander P, Deretic V (2008) Mycobacterium tuberculosis prevents inflammasome activation. Cell Host Microbe 3:224–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayer-Barber KD, Barber DL (2015) Innate and adaptive cellular immune responses to Mycobacterium tuberculosis infection. Cold Spring Harbor Perspectives in Medicine 5

    Google Scholar 

  • Mayer-Barber KD, Barber DL, Shenderov K, White SD, Wilson MS, Cheever A, Kugler D, Hieny S, Caspar P, Nunez G et al (2010) Caspase-1 independent IL-1beta production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol 184:3326–3330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayer-Barber KD, Andrade BB, Barber DL, Hieny S, Feng CG, Caspar P, Oland S, Gordon S, Sher A (2011) Innate and adaptive interferons suppress IL-1alpha and IL-1beta production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection. Immunity 35:1023–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayer-Barber KD, Andrade BB, Oland SD, Amaral EP, Barber DL, Gonzales J, Derrick SC, Shi R, Kumar NP, Wei W et al (2014) Host-directed therapy of tuberculosis based on interleukin-1 and Type I interferon crosstalk. Nature 511:99–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McElvania Tekippe E, Allen IC, Hulseberg PD, Sullivan JT, McCann JR, Sandor M, Braunstein M, Ting JP (2010) Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1. PLoS ONE 5:e12320

    Article  PubMed  PubMed Central  Google Scholar 

  • Mishra BB, Moura-Alves P, Sonawane A, Hacohen N, Griffiths G, Moita LF, Anes E (2010) Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome. Cell Microbiol 12:1046–1063

    Article  CAS  PubMed  Google Scholar 

  • 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 14:52–60

    Article  CAS  PubMed  Google Scholar 

  • Moura-Alves P, Fae K, Houthuys E, Dorhoi A, Kreuchwig A, Furkert J, Barison N, Diehl A, Munder A, Constant P et al (2014) AhR sensing of bacterial pigments regulates antibacterial defence. Nature 512:387–392

    Article  CAS  PubMed  Google Scholar 

  • Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B, van der Meer JH, van de Veerdonk FL, Ferwerda G, Heinhuis B, Devesa I et al (2009) Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood 113:2324–2335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Netea MG, van de Veerdonk FL, van der Meer JW, Dinarello CA, Joosten LA (2015) Inflammasome-independent regulation of IL-1-family cytokines. Annu Rev Immunol 33:49–77

    Article  CAS  PubMed  Google Scholar 

  • Novikov A, Cardone M, Thompson R, Shenderov K, Kirschman KD, Mayer-Barber KD, Myers TG, Rabin RL, Trinchieri G, Sher A et al (2011) Mycobacterium tuberculosis triggers host type I IFN signaling to regulate IL-1beta production in human macrophages. J Immunol 187:2540–2547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MP (2013) The immune response in tuberculosis. Annu Rev Immunol 31:475–527

    Article  PubMed  Google Scholar 

  • Philips JA, Ernst JD (2012) Tuberculosis pathogenesis and immunity. Ann Rev Pathol 7:353–384

    Article  CAS  Google Scholar 

  • Pym AS, Brodin P, Brosch R, Huerre M, Cole ST (2002) Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol Microbiol 46:709–717

    Article  CAS  PubMed  Google Scholar 

  • Renshaw PS, Panagiotidou P, Whelan A, Gordon SV, Hewinson RG, Williamson RA, Carr MD (2002) Conclusive evidence that the major T-cell antigens of the Mycobacterium tuberculosis complex ESAT-6 and CFP-10 form a tight, 1:1 complex and characterization of the structural properties of ESAT-6, CFP-10, and the ESAT-6*CFP-10 complex. Implications for pathogenesis and virulence. J Biol Chem 277:21598–21603

    Article  CAS  PubMed  Google Scholar 

  • Repasy T, Lee J, Marino S, Martinez N, Kirschner DE, Hendricks G, Baker S, Wilson AA, Kotton DN, Kornfeld H (2013) Intracellular bacillary burden reflects a burst size for Mycobacterium tuberculosis in vivo. PLoS Pathog 9:e1003190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saiga H, Kitada S, Shimada Y, Kamiyama N, Okuyama M, Makino M, Yamamoto M, Takeda K (2012) Critical role of AIM2 in Mycobacterium tuberculosis infection. Int Immunol 24:637–644

    Article  CAS  PubMed  Google Scholar 

  • Schmid-Burgk JL, Chauhan D, Schmidt T, Ebert TS, Reinhardt J, Endl E, Hornung V (2015) A genome-wide CRISPR screen identifies NEK7 as an essential component of NLRP3 inflammasome activation. J Biol Chem

    Google Scholar 

  • Shah S, Bohsali A, Ahlbrand SE, Srinivasan L, Rathinam VA, Vogel SN, Fitzgerald KA, Sutterwala FS, Briken V (2013) Cutting edge: Mycobacterium tuberculosis but not nonvirulent mycobacteria inhibits IFN-beta and AIM2 inflammasome-dependent IL-1beta production via its ESX-1 secretion system. J Immunol 191:3514–3518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah S, Cannon JR, Fenselau C, Briken V (2015) A Duplicated ESAT-6 Region of ESX-5 Is involved in protein export and virulence of Mycobacteria. Infect Immun 83:4349–4361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi CS, Shenderov K, Huang NN, Kabat J, Abu-Asab M, Fitzgerald KA, Sher A, Kehrl JH (2012) Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 13:255–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi H, Wang Y, Li X, Zhan X, Tang M, Fina M, Su L, Pratt D, Bu CH, Hildebrand S et al (2016) NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component. Nat Immunol 17:250

    Google Scholar 

  • Simeone R, Bottai D, Brosch R (2009) ESX/type VII secretion systems and their role in host-pathogen interaction. Curr Opin Microbiol 12:4–10

    Article  CAS  PubMed  Google Scholar 

  • Simeone R, Bobard A, Lippmann J, Bitter W, Majlessi L, Brosch R, Enninga J (2012) Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog 8:e1002507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srivastava S, Ernst JD, Desvignes L (2014) Beyond macrophages: the diversity of mononuclear cells in tuberculosis. Immunol Rev 262:179–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stamm CE, Collins AC, Shiloh MU (2015) Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus. Immunol Rev 264:204–219

    Article  PubMed  PubMed Central  Google Scholar 

  • Stoop EJ, Bitter W, van der Sar AM (2012) Tubercle bacilli rely on a type VII army for pathogenicity. Trends Microbiol 20:477–484

    Article  CAS  PubMed  Google Scholar 

  • Torrado E, Cooper AM (2013) Cytokines in the balance of protection and pathology during mycobacterial infections. Adv Exp Med Biol 783:121–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, Pierson J, Brenner M, Peters PJ (2007) M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell 129:1287–1298

    Article  PubMed  Google Scholar 

  • Vince JE, Wong WW, Gentle I, Lawlor KE, Allam R, O’Reilly L, Mason K, Gross O, Ma S, Guarda G et al (2012) Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity 36:215–227

    Article  CAS  PubMed  Google Scholar 

  • Walter K, Holscher C, Tschopp J, Ehlers S (2010) NALP3 is not necessary for early protection against experimental tuberculosis. Immunobiology 215:804–811

    Article  CAS  PubMed  Google Scholar 

  • Wassermann R, Gulen MF, Sala C, Perin SG, Lou Y, Rybniker J, Schmid-Burgk JL, Schmidt T, Hornung V, Cole ST et al (2015) Mycobacterium tuberculosis differentially activates cGAS- and inflammasome-dependent intracellular immune responses through ESX-1. Cell Host Microbe 17:799–810

    Article  CAS  PubMed  Google Scholar 

  • Watson RO, Manzanillo PS, Cox JS (2012) Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 150:803–815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watson RO, Bell SL, MacDuff DA, Kimmey JM, Diner EJ, Olivas J, Vance RE, Stallings CL, Virgin HW, Cox JS (2015) The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce type I interferons and activate autophagy. Cell Host Microbe 17:811–819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015, Lausanne, Switzerland

    Andrea Ablasser

  2. Max Planck Institute for Infection Biology, 10117, Berlin, Germany

    Anca Dorhoi

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  1. Andrea Ablasser
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  2. Anca Dorhoi
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Correspondence to Andrea Ablasser .

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Editors and Affiliations

  1. Department of Biology, Division of Microbiology , Friedrich Alexander University Erlangen/Nuremberg, Erlangen, Germany

    Steffen Backert

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Ablasser, A., Dorhoi, A. (2016). Inflammasome Activation and Function During Infection with Mycobacterium Tuberculosis . In: Backert, S. (eds) Inflammasome Signaling and Bacterial Infections. Current Topics in Microbiology and Immunology, vol 397. Springer, Cham. https://doi.org/10.1007/978-3-319-41171-2_9

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