The inflammasome: Learning from bacterial evasion strategies

Seminars in Immunology - Tập 27 - Trang 102-110 - 2015
Sunny Shin1, Igor E. Brodsky2
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
2Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

Tài liệu tham khảo

Janeway, 1989, Approaching the asymptote? Evolution and revolution in immunology, Cold Spring Harb. Symp. Quant. Biol., 54 Pt 1, 1, 10.1101/SQB.1989.054.01.003 Janeway, 2002, Innate immune recognition, Annu. Rev. Immunol., 20, 197, 10.1146/annurev.immunol.20.083001.084359 Kawai, 2011, Toll-like receptors and their crosstalk with other innate receptors in infection and immunity, Immunity, 34, 637, 10.1016/j.immuni.2011.05.006 Gurcel, 2006, Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival, Cell, 126, 1135, 10.1016/j.cell.2006.07.033 Lamkanfi, 2009, Inflammasomes: guardians of cytosolic sanctity, Immunol. Rev., 227, 95, 10.1111/j.1600-065X.2008.00730.x Lamkanfi, 2014, Mechanisms and functions of inflammasomes, Cell, 157, 1013, 10.1016/j.cell.2014.04.007 Davis, 2011, The inflammasome NLRs in immunity, inflammation, and associated diseases, Annu. Rev. Immunol., 29, 707, 10.1146/annurev-immunol-031210-101405 Faustin, 2007, Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation, Mol. Cell, 25, 713, 10.1016/j.molcel.2007.01.032 Martinon, 2002, The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta, Mol. Cell, 10, 417, 10.1016/S1097-2765(02)00599-3 Lu, 2014, Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes, Cell, 156, 1193, 10.1016/j.cell.2014.02.008 Dostert, 2008, Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica, Science, 320, 674, 10.1126/science.1156995 Hornung, 2010, Critical functions of priming and lysosomal damage for NLRP3 activation, Eur. J. Immunol., 40, 620, 10.1002/eji.200940185 Kahlenberg, 2004, Mechanisms of caspase-1 activation by P2X7 receptor-mediated K+ release, Am. J. Physiol. Cell Physiol., 286, C1100, 10.1152/ajpcell.00494.2003 Kanneganti, 2006, Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA, J. Biol. Chem., 281, 36560, 10.1074/jbc.M607594200 Mariathasan, 2006, Cryopyrin activates the inflammasome in response to toxins and ATP, Nature, 440, 228, 10.1038/nature04515 Martinon, 2006, Gout-associated uric acid crystals activate the NALP3 inflammasome, Nature, 440, 237, 10.1038/nature04516 Petrilli, 2007, Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration, Cell Death Differ., 14, 1583, 10.1038/sj.cdd.4402195 Wen, 2011, Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling, Nat. Immunol., 12, 408, 10.1038/ni.2022 Wen, 2012, A role for the NLRP3 inflammasome in metabolic diseases – did Warburg miss inflammation, Nat. Immunol., 13, 352, 10.1038/ni.2228 Zhou, 2011, A role for mitochondria in NLRP3 inflammasome activation, Nature, 469, 221, 10.1038/nature09663 Iyer, 2013, Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation, Immunity, 39, 311, 10.1016/j.immuni.2013.08.001 Munoz-Planillo, 2013, K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter, Immunity, 38, 1142, 10.1016/j.immuni.2013.05.016 Miao, 2006, Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf, Nat. Immunol., 7, 569, 10.1038/ni1344 Miao, 2008, Pseudomonas aeruginosa activates caspase 1 through Ipaf, Proc. Natl. Acad. Sci. U. S. A., 105, 2562, 10.1073/pnas.0712183105 Miao, 2010, Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome, Proc. Natl. Acad. Sci. U. S. A., 107, 3076, 10.1073/pnas.0913087107 Molofsky, 2006, Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection, J. Exp. Med., 203, 1093, 10.1084/jem.20051659 Ren, 2006, Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity, PLoS Pathog., 2, e18, 10.1371/journal.ppat.0020018 Sun, 2007, Injection of flagellin into the host cell cytosol by Salmonella enterica serotype Typhimurium, J. Biol. Chem., 282, 33897, 10.1074/jbc.C700181200 Sutterwala, 2007, Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome, J. Exp. Med., 204, 3235, 10.1084/jem.20071239 Yang, 2013, Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation, Proc. Natl. Acad. Sci. U. S. A., 110, 14408, 10.1073/pnas.1306376110 Zhao, 2011, The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus, Nature, 477, 596, 10.1038/nature10510 Kofoed, 2011, Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity, Nature, 477, 592, 10.1038/nature10394 Lightfield, 2008, Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin, Nat. Immunol., 9, 1171, 10.1038/ni.1646 Rayamajhi, 2013, Cutting edge: mouse NAIP1 detects the type III secretion system needle protein, J. Immunol., 191, 3986, 10.4049/jimmunol.1301549 Suzuki, 2014, Shigella type III secretion protein MxiI is recognized by Naip2 to induce Nlrc4 inflammasome activation independently of Pkcdelta, PLoS Pathog., 10, e1003926, 10.1371/journal.ppat.1003926 Zamboni, 2006, The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection, Nat. Immunol., 7, 318, 10.1038/ni1305 Broz, 2010, Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing, Cell Host Microbe, 8, 471, 10.1016/j.chom.2010.11.007 Boyden, 2006, Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin, Nat. Genet., 38, 240, 10.1038/ng1724 Cirelli, 2014, Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii, PLoS Pathog., 10, e1003927, 10.1371/journal.ppat.1003927 Ewald, 2014, NLRP1 is an inflammasome sensor for Toxoplasma gondii, Infect. Immun., 82, 460, 10.1128/IAI.01170-13 Gorfu, 2014, Dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to Toxoplasma gondii, MBio, 2014 Chavarria-Smith, 2013, Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor, PLoS Pathog., 9, e1003452, 10.1371/journal.ppat.1003452 Levinsohn, 2012, Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome, PLoS Pathog., 8, e1002638, 10.1371/journal.ppat.1002638 Guey, 2014, Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function, Proc. Natl. Acad. Sci. U. S. A., 111, 17254, 10.1073/pnas.1415756111 Witola, 2011, NALP1 influences susceptibility to human congenital toxoplasmosis, proinflammatory cytokine response, and fate of Toxoplasma gondii-infected monocytic cells, Infect. Immun., 79, 756, 10.1128/IAI.00898-10 Kayagaki, 2011, Non-canonical inflammasome activation targets caspase-11, Nature, 479, 117, 10.1038/nature10558 Broz, 2012, Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1, Nature, 490, 288, 10.1038/nature11419 Gurung, 2012, Toll or interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-beta (TRIF)-mediated caspase-11 protease production integrates Toll-like receptor 4 (TLR4) protein- and Nlrp3 inflammasome-mediated host defense against enteropathogens, J. Biol. Chem., 287, 34474, 10.1074/jbc.M112.401406 Rathinam, 2012, TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria, Cell, 10.1016/j.cell.2012.07.007 Case, 2013, Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila, Proc. Natl. Acad. Sci. U. S. A., 110, 1851, 10.1073/pnas.1211521110 Casson, 2013, Caspase-11 activation in response to bacterial secretion systems that access the host cytosol, PLoS Pathog., 9, e1003400, 10.1371/journal.ppat.1003400 Casson, 2013, Inflammasome-mediated cell death in response to bacterial pathogens that access the host cell cytosol: lessons from legionella pneumophila, Front. Cell. Infect. Microbiol., 3, 111, 10.3389/fcimb.2013.00111 Hagar, 2013, Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock, Science, 341, 1250, 10.1126/science.1240988 Kayagaki, 2013, Noncanonical inflammasome activation by intracellular LPS independent of TLR4, Science, 341, 1246, 10.1126/science.1240248 Meunier, 2014, Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases, Nature, 509, 366, 10.1038/nature13157 Pilla, 2014, Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS, Proc. Natl. Acad. Sci. U. S. A., 111, 6046, 10.1073/pnas.1321700111 Shi, 2014, Inflammatory caspases are innate immune receptors for intracellular LPS, Nature, 514, 187, 10.1038/nature13683 Knodler, 2014, Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens, Cell Host Microbe, 16, 249, 10.1016/j.chom.2014.07.002 Wang, 1998, Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE, Cell, 92, 501, 10.1016/S0092-8674(00)80943-5 von Moltke, 2013, Recognition of bacteria by inflammasomes, Annu. Rev. Immunol., 31, 73, 10.1146/annurev-immunol-032712-095944 Taxman, 2010, Inflammasome inhibition as a pathogenic stealth mechanism, Cell Host Microbe, 8, 7, 10.1016/j.chom.2010.06.005 Palm, 2013, Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity, Immunity, 39, 976, 10.1016/j.immuni.2013.10.006 Galle, 2008, The Pseudomonas aeruginosa Type III secretion system plays a dual role in the regulation of caspase-1 mediated IL-1beta maturation, J. Cell. Mol. Med., 12, 1767, 10.1111/j.1582-4934.2007.00190.x Schotte, 2004, Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta, J. Biol. Chem., 279, 25134, 10.1074/jbc.M401245200 Hoffmann, 2010, In macrophages, caspase-1 activation by SopE and the type III secretion system-1 of S. typhimurium can proceed in the absence of flagellin, PLoS ONE, 5, e12477, 10.1371/journal.pone.0012477 Muller, 2009, The S. Typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation, Cell Host Microbe, 6, 125, 10.1016/j.chom.2009.07.007 Fu, 1999, A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion, Nature, 401, 293, 10.1038/45829 Hardt, 1998, S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells, Cell, 93, 815, 10.1016/S0092-8674(00)81442-7 Raffatellu, 2009, Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine, Cell Host Microbe, 5, 476, 10.1016/j.chom.2009.03.011 Winter, 2010, Gut inflammation provides a respiratory electron acceptor for Salmonella, Nature, 467, 426, 10.1038/nature09415 Hornung, 2008, Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization, Nat. Immunol., 9, 847, 10.1038/ni.1631 Bruno, 2009, Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells, PLoS Pathog., 5, e1000538, 10.1371/journal.ppat.1000538 Keestra, 2013, Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1, Nature, 496, 233, 10.1038/nature12025 LaRock, 2012, The Yersinia virulence effector YopM binds caspase-1 to arrest inflammasome assembly and processing, Cell Host Microbe, 12, 799, 10.1016/j.chom.2012.10.020 Miao, 1999, Salmonella typhimurium leucine-rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems, Mol. Microbiol., 34, 850, 10.1046/j.1365-2958.1999.01651.x Leung, 1990, YopM inhibits platelet aggregation and is necessary for virulence of Yersinia pestis in mice, Infect. Immun., 58, 3262, 10.1128/IAI.58.10.3262-3271.1990 McPhee, 2012, Interleukin-10 induction is an important virulence function of the Yersinia pseudotuberculosis type III effector YopM, Infect. Immun., 80, 2519, 10.1128/IAI.06364-11 Boland, 1998, Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during Yersinia infection, Infect. Immun., 66, 1878, 10.1128/IAI.66.5.1878-1884.1998 Chung, 2014, IQGAP1 is important for activation of caspase-1 in macrophages and is targeted by Yersinia pestis type III effector YopM, MBio, 5, e01402, 10.1128/mBio.01402-14 Jameson, 2013, IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors, Nat. Med., 19, 626, 10.1038/nm.3165 McLaughlin, 2009, The Salmonella SPI2 effector SseI mediates long-term systemic infection by modulating host cell migration, PLoS Pathog., 5, e1000671, 10.1371/journal.ppat.1000671 Philip, 2014, Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-kappaB and MAPK signaling, Proc. Natl. Acad. Sci. U. S. A., 111, 7385, 10.1073/pnas.1403252111 Weng, 2014, Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death, Proc. Natl. Acad. Sci. U. S. A., 111, 7391, 10.1073/pnas.1403477111 Fernandes-Alnemri, 2009, AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA, Nature, 10.1038/nature07710 Hornung, 2009, AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC, Nature, 10.1038/nature07725 Jones, 2010, Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis, Proc. Natl. Acad. Sci. U. S. A., 107, 9771, 10.1073/pnas.1003738107 Peng, 2011, Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis, Cell. Microbiol., 13, 1586, 10.1111/j.1462-5822.2011.01643.x Rathinam, 2010, The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses, Nat. Immunol., 11, 395, 10.1038/ni.1864 Sauer, 2010, Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol, Cell Host Microbe, 7, 412, 10.1016/j.chom.2010.04.004 Warren, 2010, Cutting edge: cytosolic bacterial DNA activates the inflammasome via Aim2, J. Immunol., 185, 818, 10.4049/jimmunol.1000724 Yang, 2013, the AIM2 inflammasome is involved in macrophage activation during infection with virulent Mycobacterium bovis strain, J. Infect. Dis., 208, 1849, 10.1093/infdis/jit347 Shah, 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, 10.4049/jimmunol.1301331 Carlsson, 2010, Host-detrimental role of Esx-1-mediated inflammasome activation in mycobacterial infection, PLoS Pathog., 6, e1000895, 10.1371/journal.ppat.1000895 Koo, 2008, ESX-1-dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection, Cell. Microbiol., 10, 1866, 10.1111/j.1462-5822.2008.01177.x Mishra, 2010, Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome, Cell. Microbiol., 12, 1046, 10.1111/j.1462-5822.2010.01450.x Le, 2013, Pyrin- and CARD-only proteins as regulators of NLR functions, Front. Immunol., 4, 275, 10.3389/fimmu.2013.00275 Johnston, 2005, A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection, Immunity, 23, 587, 10.1016/j.immuni.2005.10.003 Rahman, 2009, Co-regulation of NF-kappaB and inflammasome-mediated inflammatory responses by myxoma virus pyrin domain-containing protein M013, PLoS Pathog., 5, e1000635, 10.1371/journal.ppat.1000635 Gregory, 2011, Discovery of a viral NLR homolog that inhibits the inflammasome, Science, 331, 330, 10.1126/science.1199478 Ichinohe, 2010, Influenza virus activates inflammasomes via its intracellular M2 ion channel, Nat. Immunol., 11, 404, 10.1038/ni.1861 Kobayashi, 2013, The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection, Cell Host Microbe, 13, 570, 10.1016/j.chom.2013.04.012 Hajjar, 2012, Humanized TLR4/MD-2 mice reveal LPS recognition differentially impacts susceptibility to Yersinia pestis and Salmonella enterica, PLoS Pathog., 8, e1002963, 10.1371/journal.ppat.1002963 Montminy, 2006, Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response, Nat. Immunol., 7, 1066, 10.1038/ni1386 Rebeil, 2004, Variation in lipid A structure in the pathogenic yersiniae, Mol. Microbiol., 52, 1363, 10.1111/j.1365-2958.2004.04059.x Hammer, 1999, Co-ordination of legionella pneumophila virulence with entry into stationary phase by ppGpp, Mol. Microbiol., 33, 721, 10.1046/j.1365-2958.1999.01519.x Iyoda, 2001, A flagellar gene fliZ regulates the expression of invasion genes and virulence phenotype in Salmonella enterica serovar Typhimurium, Microb. Pathog., 30, 81, 10.1006/mpat.2000.0409 Lucas, 2000, Multiple factors independently regulate hilA and invasion gene expression in Salmonella enterica serovar typhimurium, J. Bacteriol., 182, 1872, 10.1128/JB.182.7.1872-1882.2000 Cummings, 2006, In vivo, fliC expression by Salmonella enterica serovar Typhimurium is heterogeneous, regulated by ClpX, and anatomically restricted, Mol. Microbiol., 61, 795, 10.1111/j.1365-2958.2006.05271.x Winter, 2010, A rapid change in virulence gene expression during the transition from the intestinal lumen into tissue promotes systemic dissemination of Salmonella, PLoS Pathog., 6, e1001060, 10.1371/journal.ppat.1001060 Franchi, 2012, NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense, Nat. Immunol., 10.1038/ni.2263 Miao, 2010, Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria, Nat. Immunol., 11, 1136, 10.1038/ni.1960 Minnich, 2007, A rationale for repression and/or loss of motility by pathogenic Yersinia in the mammalian host, Adv. Exp. Med. Biol., 603, 298, 10.1007/978-0-387-72124-8_27 Chain, 2004, Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis, Proc. Natl. Acad. Sci. U. S. A., 101, 13826, 10.1073/pnas.0404012101 Perez-Lopez, 2013, Salmonella downregulates Nod-like receptor family CARD domain containing protein 4 expression to promote its survival in B cells by preventing inflammasome activation and cell death, J. Immunol., 190, 1201, 10.4049/jimmunol.1200415 Abdelaziz, 2011, Apoptosis-associated speck-like protein (ASC) controls Legionella pneumophila infection in human monocytes, J. Biol. Chem., 286, 3203, 10.1074/jbc.M110.197681 Brodsky, 2010, A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system, Cell Host Microbe, 7, 376, 10.1016/j.chom.2010.04.009 Holmstrom, 1997, YopK of Yersinia pseudotuberculosis controls translocation of Yop effectors across the eukaryotic cell membrane, Mol. Microbiol., 24, 73, 10.1046/j.1365-2958.1997.3211681.x Kwuan, 2013, Impact of host membrane pore formation by the Yersinia pseudotuberculosis type III secretion system on the macrophage innate immune response, Infect. Immun., 81, 905, 10.1128/IAI.01014-12 Zwack, 2014, Inflammasome activation in response to the Yersinia type III secretion system requires hyperinjection of translocon proteins YopB and YopD, MBio, 2014 Collazo, 1997, The invasion-associated type III system of Salmonella typhimurium directs the translocation of Sip proteins into the host cell, Mol. Microbiol., 24, 747, 10.1046/j.1365-2958.1997.3781740.x Francis, 1998, YopD of Yersinia pseudotuberculosis is translocated into the cytosol of HeLa epithelial cells: evidence of a structural domain necessary for translocation, Mol. Microbiol., 29, 799, 10.1046/j.1365-2958.1998.00973.x Hersh, 1999, The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1, Proc. Natl. Acad. Sci. U. S. A., 96, 2396, 10.1073/pnas.96.5.2396 Edqvist, 2007, Minimal YopB and YopD translocator secretion by Yersinia is sufficient for Yop-effector delivery into target cells, Microbes Infect., 9, 224, 10.1016/j.micinf.2006.11.010 Dewoody, 2011, YopK regulates the Yersinia pestis type III secretion system from within host cells, Mol. Microbiol., 79, 1445, 10.1111/j.1365-2958.2011.07534.x Thorslund, 2011, The RACK1 signaling scaffold protein selectively interacts with Yersinia pseudotuberculosis virulence function, PLoS ONE, 6, e16784, 10.1371/journal.pone.0016784 Brodsky, 2008, Reduced secretion of YopJ by Yersinia limits in vivo cell death but enhances bacterial virulence, PLoS Pathog., 4, e1000067, 10.1371/journal.ppat.1000067 Zauberman, 2009, Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague, PLoS ONE, 4, e5938, 10.1371/journal.pone.0005938 Blander, 2012, Beyond pattern recognition: five immune checkpoints for scaling the microbial threat, Nat. Rev. Immunol., 12, 215, 10.1038/nri3167 Sander, 2011, Detection of prokaryotic mRNA signifies microbial viability and promotes immunity, Nature, 474, 385, 10.1038/nature10072 Vance, 2009, Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system, Cell Host Microbe, 6, 10, 10.1016/j.chom.2009.06.007 Chang, 2014, The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition, Proc. Natl. Acad. Sci. U. S. A., 111, 2247, 10.1073/pnas.1322269111 Arpaia, 2013, Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation, Nature, 504, 451, 10.1038/nature12726 Furusawa, 2013, Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells, Nature, 504, 446, 10.1038/nature12721 Smith, 2013, The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis, Science, 341, 569, 10.1126/science.1241165 Wynosky-Dolfi, 2014, Oxidative metabolism enables Salmonella evasion of the NLRP3 inflammasome, J. Exp. Med., 211, 653, 10.1084/jem.20130627 Lawley, 2006, Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse, PLoS Pathog., 2, e11, 10.1371/journal.ppat.0020011 Fang, 2005, Isocitrate lyase (AceA) is required for Salmonella persistence but not for acute lethal infection in mice, Infect. Immun., 73, 2547, 10.1128/IAI.73.4.2547-2549.2005 McKinney, 2000, Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase, Nature, 406, 735, 10.1038/35021074 Egan, 2014, The SPI-1-like Type III secretion system: more roles than you think, Front. Plant Sci., 5, 34, 10.3389/fpls.2014.00034 Ayres, 2012, Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota, Nat. Med., 18, 799, 10.1038/nm.2729 West, 2011, Mitochondria in innate immune responses, Nat. Rev. Immunol., 11, 389, 10.1038/nri2975