Integrative inflammasome activity in the regulation of intestinal mucosal immune responses

被引:80
作者
Elinav, E. [1 ]
Henao-Mejia, J. [1 ]
Flavell, R. A. [1 ]
机构
[1] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Immunobiol, New Haven, CT 06510 USA
关键词
NF-KAPPA-B; ULCERATIVE-COLITIS; COLORECTAL-CANCER; CROHNS-DISEASE; TNF-ALPHA; NLRP3; INFLAMMASOME; COLON INFLAMMATION; MURINE COLITIS; HOST-DEFENSE; ACTIVATION;
D O I
10.1038/mi.2012.115
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The mammalian intestinal tract harbors a vast and diverse ecosystem of microbes that are separated from the sterile host milieu by a single layer of epithelial cells. While this bio-geographical configuration is critical for host biological processes, it imposes a risk for microbial penetration and life-threatening systemic invasion. Inflammasomes are cytosolic multi-protein platforms that sense both microbial and damage-associated molecular patterns and initiate a potent innate immune anti-microbial response. In this review, we will highlight the role of inflammasomes in the orchestration and regulation of the intestinal immune response, focusing on the roles of inflammasomes in maintenance of intestinal homeostasis, enteric infection, auto-inflammation, and tumorigenesis. We highlight the centrality of inflammasome signaling in the complex cross-talk between host mucosal immune arms and the environment, in particular the microflora, with emphasis on the spatial and temporal integration of inflammasome activation with signals from other innate signaling platforms.
引用
收藏
页码:4 / 13
页数:10
相关论文
共 77 条
[1]   NLRP12 Suppresses Colon Inflammation and Tumorigenesis through the Negative Regulation of Noncanonical NF-κB Signaling [J].
Allen, Irving C. ;
Wilson, Justin E. ;
Schneider, Monika ;
Lich, John D. ;
Roberts, Reid A. ;
Arthur, Janelle C. ;
Woodford, Rita-Marie T. ;
Davis, Beckley K. ;
Uronis, Joshua M. ;
Herfarth, Hans H. ;
Jobin, Christian ;
Rogers, Arlin B. ;
Ting, Jenny P. -Y. .
IMMUNITY, 2012, 36 (05) :742-754
[2]   The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer [J].
Allen, Irving C. ;
TeKippe, Erin McElvania ;
Woodford, Rita-Marie T. ;
Uronis, Joshua M. ;
Holl, Eda K. ;
Rogers, Arlin B. ;
Herfarth, Hans H. ;
Jobin, Christian ;
Ting, Jenny P. -Y. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (05) :1045-1056
[3]   Lethal inflammasome activation by a multidrug- resistant pathobiont upon antibiotic disruption of the microbiota [J].
Ayres, Janelle S. ;
Trinidad, Norver J. ;
Vance, Russell E. .
NATURE MEDICINE, 2012, 18 (05) :799-U201
[4]   Linkage of gut microbiome with cognition in hepatic encephalopathy [J].
Bajaj, Jasmohan S. ;
Ridlon, Jason M. ;
Hylemon, Phillip B. ;
Thacker, Leroy R. ;
Heuman, Douglas M. ;
Smith, Sean ;
Sikaroodi, Masoumeh ;
Gillevet, Patrick M. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2012, 302 (01) :G168-G175
[5]   The ICE inhibitor pralnacasan prevents DSS-induced colitis in C57BL/6 mice and suppresses IP-10 mRNA but not TNF-α mRNA expression [J].
Bauer, Christian ;
Loher, Florian ;
Dauer, Marc ;
Mayer, Christine ;
Lehr, Hans Anton ;
Schoenharting, Martin ;
Hallwachs, Roland ;
Endres, Stefan ;
Eigler, Andreas .
DIGESTIVE DISEASES AND SCIENCES, 2007, 52 (07) :1642-1652
[6]   Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome [J].
Bauer, Christian ;
Duewell, Peter ;
Mayer, Christine ;
Lehr, Hans Anton ;
Fitzgerald, Katherine A. ;
Dauer, Marc ;
Tschopp, Jurg ;
Endres, Stefan ;
Latz, Eicke ;
Schnurr, Max .
GUT, 2010, 59 (09) :1192-1199
[7]   TGF-β suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling [J].
Becker, C ;
Fantini, MC ;
Schramm, C ;
Lehr, HA ;
Wirtz, S ;
Nikolaev, A ;
Burg, J ;
Strand, S ;
Kiesslich, R ;
Huber, S ;
Ito, H ;
Nishimoto, N ;
Yoshizaki, K ;
Nishimoto, N ;
Galle, PR ;
Blessing, M ;
Rose-John, S ;
Neurath, MF .
IMMUNITY, 2004, 21 (04) :491-501
[8]   gp130-Mediated Stat3 Activation in Enterocytes Regulates Cell Survival and Cell-Cycle Progression during Colitis-Associated Tumorigenesis [J].
Bollrath, Julia ;
Phesse, Toby J. ;
von Burstin, Vivian A. ;
Putoczki, Tracy ;
Bennecke, Moritz ;
Bateman, Trudie ;
Nebelsiek, Tim ;
Lundgren-May, Therese ;
Canli, Oezge ;
Schwitalla, Sarah ;
Matthews, Vance ;
Schmid, Roland M. ;
Kirchner, Thomas ;
Arkan, Melek C. ;
Ernst, Matthias ;
Greten, Florian R. .
CANCER CELL, 2009, 15 (02) :91-102
[9]   Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella [J].
Broz, Petr ;
Newton, Kim ;
Lamkanfi, Mohamed ;
Mariathasan, Sanjeev ;
Dixit, Vishva M. ;
Monack, Denise M. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (08) :1745-1755
[10]   A Functional Role for Nlrp6 in Intestinal Inflammation and Tumorigenesis [J].
Chen, Grace Y. ;
Liu, Maochang ;
Wang, Fuyuan ;
Bertin, John ;
Nunez, Gabriel .
JOURNAL OF IMMUNOLOGY, 2011, 186 (12) :7187-7194