细胞焦亡、炎症小体Inflammasomes

DNA viruses mCMV Vaccinia Herpes viruses Cytosolic bacteria Francisella tularensis Listeria monocyotgenes ASC KSHV DNA AIM2 IFI16 NUCLEUS NUCLEUS Signal 1 ASC NLR or ALR Active caspase-1 IL-1b IL-18 Signal 2 RECEPTOR ADAPTOR EFFECTOR Infl ammasome complex Basic infl ammasome structure ASC NLRP6NLRP12 Microbes ? (In human monocytes ALR, AIM2-like receptor; ASC, apoptotic speck-like protein containing CARD; ATP, adenosine triphosphate; CARD, caspase-1 activation and recruitment domain; CASR, calcium-sensing receptor; ER, endoplasmic reticulum; GBP5, guanylate-binding protein 5; HMGB1, high mobility group B1; ICE, IL-1-converting enzyme; IFI16, interferon inducible protein 16; IL-1, interleukin 1; InsP3, inositol-1,3,5 triphosphate; KSHV, Kaposi-sarcoma-associated herpes virus; LF, lethal factor; LT, lethal toxin; MAMP, microbe-associated molecular pattern; NLR, NOD-like receptors; PA, protective antigen; PLC, phospholipase C; PRR, pattern recognition receptor; PYD, pyrin domain; PYHIN, pyrin and HIN200 domain containing; ROS, reactive oxygen species; TLR, Toll-like receptor; TRIF, Toll/interleukin-1 receptor (TIR)-domain-containing adaptor inducing IFN-. Acknowledgments We apologize to the colleagues whose work could not be cited here because of space limitations. RefeRences Elinav, E., Strowig, T., Kau, A.L., Henao-Mejia, J., Thaiss, C.A., Booth, C.J., Peaper, D.R., Bertin, J., Eisenbarth, S.C., Gordon, J.I., and Flavell, R.A. (2011). NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145, 745757. Fernandes-Alnemri, T., Yu, J.W., Juliana, C., Solorzano, L., Kang, S., Wu, J., Datta, P., McCormick, M., Huang, L., McDermott, E., et al. (2010). The AIM2 inflammasome is critical for innate im- munity to Francisella tularensis. Nat. Immunol. 11, 385393. Kerur, N., Veettil, M.V., Sharma-Walia, N., Bottero, V., Sadagopan, S., Otageri, P., and Chandran, B. (2011). IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection. Cell Host Microbe 9, 363375. Khare, S., Dorfleutner, A., Bryan, N.B., Yun, C., Radian, A.D., de Almeida, L., Rojanasakul, Y., and Stehlik, C. (2012). An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages. Immunity 36, 464476. Kofoed, E.M., and Vance, R.E. (2011). Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity. Nature 477, 592595. Qu, Y., Misaghi, S., Izrael-Tomasevic, A., Newton, K., Gilmour, L.L., Lamkanfi, M., Louie, S., Kayagaki, N., Liu, J., Kmves, L., et al. (2012). Phosphorylation of NLRC4 is critical for inflam- masome activation. Nature 490, 539542. Rathinam, V.A., Jiang, Z., Waggoner, S.N., Sharma, S., Cole, L.E., Waggoner, L., Vanaja, S.K., Monks, B.G., Ganesan, S., Latz, E., et al. (2010). The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395402. Rathinam, V.A., Vanaja, S.K., Waggoner, L., Sokolovska, A., Becker, C., Stuart, L.M., Leong, J.M., and Fitzgerald, K.A. (2012). TRIF licenses caspase-11-dependent NLRP3 inflammasome activa- tion by gram-negative bacteria. Cell 150, 606619. Shenoy, A.R., Wellington, D.A., Kumar, P., Kassa, H., Booth, C.J., Cresswell, P., and MacMicking, J.D. (2012). GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Sci- ence 336, 481485. Vladimer, G.I., Weng, D., Paquette,