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Inflammasome

Editor-in-Chief: Pelegrin, Pablo

Ed. by Lopez-Castejón, Gloria


Emerging Science

Open Access
Online
ISSN
2300-102X
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Signaling cascades and inflammasome activation in microbial infections

Syed Raza Ali1 / Michael Karin23 / Victor Nizet14

1Department of Pediatrics

2Laboratory of Signal Transduction, Department of Pharmacology

3Department of Pathology

4Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA

© 2015 Syed Raza Ali et al.. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)

Citation Information: Inflammasome. Volume 2, Issue 1, Pages 7–12, ISSN (Online) 2300-102X, DOI: https://doi.org/10.1515/infl-2015-0002, February 2015

Publication History

Received:
2014-09-23
Accepted:
2015-01-07
Published Online:
2015-02-02

Abstract

Recognition of extracellular pathogenassociated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) results in activation of host defense signaling pathways. Some virulent microbes can attenuate and escape antimicrobial immunity by manipulating these signaling pathways. However, impairment of the primary innate response may potentiate the activation of secondary defense program, centered around Nucleotide-binding domain and Leucine-rich repeat containing Receptor (NLRs) for inflammasome formation and IL-1β production. This review analyzes the current knowledge regarding association of innate immune signaling pathways with inflammasome activation in response to bacterial infection.

Keywords : inflammasome; signaling; NLR; p38; AKT; Bcl2; cIAP; MAPK; pathogen; anthrax

References

  • [1] Franchi, L., Munoz-Planillo, R., and Nunez, G. (2012). Sensing and reacting to microbes through the inflammasomes. Nat Immunol 13, 325-332. [Web of Science] [Crossref]

  • [2] Lamkanfi, M., and Dixit, V.M. (2012). Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol 28, 137-161. [Crossref]

  • [3] Larock, C.N., and Cookson, B.T. (2013). Burning Down the House: Cellular Actions during Pyroptosis. PLoS Pathog 9, e1003793. [Web of Science] [Crossref]

  • [4] Schroder, K., and Tschopp, J. (2010). The inflammasomes. Cell 140, 821-832. [Web of Science]

  • [5] Rathinam, V.A., Vanaja, S.K., and Fitzgerald, K.A. (2012). Regulation of inflammasome signaling. Nat Immunol 13, 333-332. [Crossref]

  • [6] Broz, P., and Monack, D.M. (2011). Molecular mechanisms of inflammasome activation during microbial infections. Immunol Rev 243, 174-190. [Web of Science]

  • [7] Hsu, L.C., Ali, S.R., McGillivray, S., Tseng, P.H., Mariathasan, S., Humke, E.W., Eckmann, L., Powell, J.J., Nizet, V., Dixit, V.M., et al. (2008). A NOD2-NALP1 complex mediates caspase-1- dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A 105, 7803-7808.

  • [8] Vladimer, G.I., Weng, D., Paquette, S.W., Vanaja, S.K., Rathinam, V.A., Aune, M.H., Conlon, J.E., Burbage, J.J., Proulx, M.K., Liu, Q., et al. (2012). The NLRP12 inflammasome recognizes Yersinia pestis. Immunity 37, 96-107.

  • [9] Lamkanfi, M., and Dixit, V.M. (2014). Mechanisms and functions of inflammasomes. Cell 157, 1013-1022.

  • [10] Park, J.M., Greten, F.R., Li, Z.W., and Karin, M. (2002). Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 297, 2048-2051.

  • [11] Krachler, A.M., Woolery, A.R., and Orth, K. (2011). Manipulation of kinase signaling by bacterial pathogens. J Cell Biol 195, 1083-1092. [Web of Science]

  • [12] Ali, S.R., Timmer, A.M., Bilgrami, S., Park, E.J., Eckmann, L., Nizet, V., and Karin, M. (2011). Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakage. Immunity 35, 34-44. [Web of Science] [Crossref]

  • [13] Guichard, A., Nizet, V., and Bier, E. (2012). New insights into the biological effects of anthrax toxins: linking cellular to organismal responses. Microbes Infect 14, 97-118. [Web of Science] [Crossref]

  • [14] Moayeri, M., Sastalla, I., and Leppla, S.H. (2012). Anthrax and the inflammasome. Microbes Infect 14, 392-400. [Crossref]

  • [15] Ngai, S., Batty, S., Liao, K.C., and Mogridge, J. (2010). An anthrax lethal factor mutant that is defective at causing pyroptosis retains proapoptotic activity. FEBS J 277, 119-127. [Web of Science]

  • [16] Park, J.M., Greten, F.R., Wong, A., Westrick, R.J., Arthur, J.S., Otsu, K., Hoffmann, A., Montminy, M., and Karin, M. (2005). Signaling pathways and genes that inhibit pathogeninduced macrophage apoptosis--CREB and NF-kappaB as key regulators. Immunity 23, 319-329. [Crossref]

  • [17] Chuang, S.Y., Yang, C.H., Chou, C.C., Chiang, Y.P., Chuang, T.H., and Hsu, L.C. (2013). TLR-induced PAI-2 expression suppresses IL-1beta processing via increasing autophagy and NLRP3 degradation. Proc Natl Acad Sci U S A 110, 16079-16084.

  • [18] Pan, Q., Mathison, J., Fearns, C., Kravchenko, V.V., Da Silva Correia, J., Hoffman, H.M., Kobayashi, K.S., Bertin, J., Grant, E.P., Coyle, A.J., et al. (2007). MDP-induced interleukin-1beta processing requires Nod2 and CIAS1/NALP3. J Leukoc Biol 82, 177-183. [Crossref]

  • [19] Clark, N.M., Marinis, J.M., Cobb, B.A., and Abbott, D.W. (2008). MEKK4 sequesters RIP2 to dictate NOD2 signal specificity. Curr Biol 18, 1402-1408. [Crossref]

  • [20] Zhang, Z., Wu, Y., Gao, M., Zhang, J., Kong, Q., Liu, Y., Ba, H., Zhou, J., and Zhang, Y. (2012). Disruption of PAMP-induced MAP kinase cascade by a Pseudomonas syringae effector activates plant immunity mediated by the NB-LRR protein SUMM2. Cell Host Microbe 11, 253-263. [Crossref] [Web of Science]

  • [21] Pitzschke, A., Schikora, A., and Hirt, H. (2009). MAPK cascade signalling networks in plant defence. Curr Opin Plant Biol 12, 421-426. [Web of Science] [Crossref]

  • [22] Vallabhapurapu, S., and Karin, M. (2009). Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27, 693-733. [Crossref]

  • [23] Ashida, H., Kim, M., Schmidt-Supprian, M., Ma, A., Ogawa, M., and Sasakawa, C. (2010). A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response. Nat Cell Biol 12, 66-73; sup pp 61-69. [Crossref] [Web of Science]

  • [24] Nadler, C., Baruch, K., Kobi, S., Mills, E., Haviv, G., Farago, M., Alkalay, I., Bartfeld, S., Meyer, T.F., Ben-Neriah, Y., et al. (2010). The type III secretion effector NleE inhibits NF-kappaB activation. PLoS Pathog 6, e1000743. [Crossref]

  • [25] Greten, F.R., Arkan, M.C., Bollrath, J., Hsu, L.C., Goode, J., Miething, C., Goktuna, S.I., Neuenhahn, M., Fierer, J., Paxian, S., et al. (2007). NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell 130, 918-931.

  • [26] Hsu, L.C., Enzler, T., Seita, J., Timmer, A.M., Lee, C.Y., Lai, T.Y., Yu, G.Y., Lai, L.C., Temkin, V., Sinzig, U., et al. (2011). IL-1beta-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKbeta. Nat Immunol 12, 144-150. [Web of Science] [Crossref]

  • [27] Zheng, Y., Lilo, S., Brodsky, I.E., Zhang, Y., Medzhitov, R., Marcu, K.B., and Bliska, J.B. (2011). A Yersinia effector with enhanced inhibitory activity on the NF-kappaB pathway activates the NLRP3/ASC/caspase-1 inflammasome in macrophages. PLoS Pathog 7, e1002026. [Crossref] [Web of Science]

  • [28] Hsu, L.C., Park, J.M., Zhang, K., Luo, J.L., Maeda, S., Kaufman, R.J., Eckmann, L., Guiney, D.G., and Karin, M. (2004). The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428, 341-345.

  • [29] Lu, B., Nakamura, T., Inouye, K., Li, J., Tang, Y., Lundback, P., Valdes-Ferrer, S.I., Olofsson, P.S., Kalb, T., Roth, J., et al. (2012). Novel role of PKR in inflammasome activation and HMGB1 release. Nature 488, 670-674.

  • [30] Stunden, H.J., and Latz, E. (2013). PKR stirs up inflammasomes. Cell Res 23, 168-170. [Crossref] [Web of Science]

  • [31] Shu, S. (2010). Molecular Mechanism of AGC Kinases in Human Malignant. Theses, Univ of South Florida

  • [32] Ivanov, S.S., and Roy, C.R. (2013). Pathogen signatures activate a ubiquitination pathway that modulates the function of the metabolic checkpoint kinase mTOR. Nat Immunol 14, 1219-1228. [Web of Science] [Crossref]

  • [33] Ge, J., Gong, Y.N., Xu, Y., and Shao, F. (2012). Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc Natl Acad Sci U S A 109, 6193-6198. [Web of Science]

  • [34] Xu, H., Yang, J., Gao, W., Li, L., Li, P., Zhang, L., Gong, Y.N., Peng, X., Xi, J.J., Chen, S., et al. (2014). Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature 513, 237-241. [Web of Science]

  • [35] Keestra, A.M., Winter, M.G., Auburger, J.J., Frassle, S.P., Xavier, M.N., Winter, S.E., Kim, A., Poon, V., Ravesloot, M.M., Waldenmaier, J.F., et al. (2013). Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature 496, 233-237. [Web of Science]

  • [36] Labbe, K., McIntire, C.R., Doiron, K., Leblanc, P.M., and Saleh, M. (2011). Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome. Immunity 35, 897-907. [Crossref] [Web of Science]

  • [37] Vince, J.E., Wong, W.W., Gentle, I., Lawlor, K.E., Allam, R., O’Reilly, L., Mason, K., Gross, O., Ma, S., Guarda, G., et al. (2012). Inhibitor of apoptosis proteins limit RIP3 kinasedependent interleukin-1 activation. Immunity 36, 215-227. [Web of Science] [Crossref]

  • [38] Bauler, L.D., Duckett, C.S., and O’Riordan, M.X. (2008). XIAP regulates cytosol-specific innate immunity to Listeria infection. PLoS Pathog 4, e1000142. [Crossref]

  • [39] Krieg, A., and Reed, J.C. (2010). IAPs and their emergent role in NLR signaling. Cell Cycle 9, 426-427. [Web of Science] [Crossref]

  • [40] Bruey, J.M., Bruey-Sedano, N., Luciano, F., Zhai, D., Balpai, R., Xu, C., Kress, C.L., Bailly-Maitre, B., Li, X., Osterman, A., et al. (2007). Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell 129, 45-56.

  • [41] Faustin, B., Lartigue, L., Bruey, J.M., Luciano, F., Sergienko, E., Bailly-Maitre, B., Volkmann, N., Hanein, D., Rouiller, I., and Reed, J.C. (2007). Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell 25, 713-724. [Crossref]

  • [42] Yeretssian, G., Correa, R.G., Doiron, K., Fitzgerald, P., Dillon, C.P., Green, D.R., Reed, J.C., and Saleh, M. (2011). Non-apoptotic role of BID in inflammation and innate immunity. Nature 474, 96-99.

  • [43] Spector, M.S., Desnoyers, S., Hoeppner, D.J., and Hengartner, M.O. (1997). Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 385, 653-656.

  • [44] Shimada, K., Crother, T.R., Karlin, J., Dagvadorj, J., Chiba, N., Chen, S., Ramanujan, V.K., Wolf, A.J., Vergnes, L., Ojcius, D.M., et al. (2012). Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36, 401-414. [Web of Science] [Crossref]

  • [45] Baroja-Mazo, A., Martin-Sanchez, F., Gomez, A.I., Martinez, C.M., Amores-Iniesta, J., Compan, V., Barbera-Cremades, M., Yague, J., Ruiz-Ortiz, E., Anton, J., et al. (2014). The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol 15, 738-748. [Crossref] [Web of Science]

  • [46] Franklin, B.S., Bossaller, L., De Nardo, D., Ratter, J.M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S.R., Al-Amoudi, A., et al. (2014). The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation. Nat Immunol 15, 727-737. [Web of Science] [Crossref]

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