Evasion of Inflammasome Activation by Microbial Pathogens

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2015 Feb 3

PMID 25642707

Citations 41

Authors

Tyler K Ulland

Polly J Ferguson

Fayyaz S Sutterwala

Affiliations

Soon will be listed here.

Abstract

Activation of the inflammasome occurs in response to infection with a wide array of pathogenic microbes. The inflammasome serves as a platform to activate caspase-1, which results in the subsequent processing and secretion of the proinflammatory cytokines IL-1β and IL-18 and the initiation of an inflammatory cell death pathway termed pyroptosis. Effective inflammasome activation is essential in controlling pathogen replication as well as initiating adaptive immune responses against the offending pathogens. However, a number of pathogens have developed strategies to evade inflammasome activation. In this Review, we discuss these pathogen evasion strategies as well as the potential infectious complications of therapeutic blockade of IL-1 pathways.

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References

Feltman H, Schulert G, Khan S, Jain M, Peterson L, Hauser A . Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa. Microbiology (Reading). 2001; 147(Pt 10):2659-2669. DOI: 10.1099/00221287-147-10-2659. View

Keane J, Gershon S, Wise R, Kasznica J, Schwieterman W, Siegel J . Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001; 345(15):1098-104. DOI: 10.1056/NEJMoa011110. View

Cohen S, Hurd E, Cush J, Schiff M, Weinblatt M, Moreland L . Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002; 46(3):614-24. DOI: 10.1002/art.10141. View

Nuki G, Bresnihan B, Bear M, McCabe D . Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin-1 receptor antagonist) in patients with rheumatoid arthritis: extension phase of a randomized, double-blind, placebo-controlled.... Arthritis Rheum. 2002; 46(11):2838-46. DOI: 10.1002/art.10578. View

Fleischmann R, Schechtman J, Bennett R, Handel M, Burmester G, Tesser J . Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum. 2003; 48(4):927-34. DOI: 10.1002/art.10870. View

Marshall J . Such stuff as dreams are made on: mediator-directed therapy in sepsis. Nat Rev Drug Discov. 2003; 2(5):391-405. DOI: 10.1038/nrd1084. View

Ray C, Black R, Kronheim S, Greenstreet T, Sleath P, Salvesen G . Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992; 69(4):597-604. DOI: 10.1016/0092-8674(92)90223-y. View

Schotte P, Denecker G, Van Den Broeke A, Vandenabeele P, Cornelis G, Beyaert R . Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta. J Biol Chem. 2004; 279(24):25134-42. DOI: 10.1074/jbc.M401245200. View

Cohen S, Moreland L, Cush J, Greenwald M, Block S, Shergy W . A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate. Ann Rheum Dis. 2004; 63(9):1062-8. PMC: 1755108. DOI: 10.1136/ard.2003.016014. View

10.

Genovese M, Cohen S, Moreland L, Lium D, Robbins S, Newmark R . Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum. 2004; 50(5):1412-9. DOI: 10.1002/art.20221. View

11.

Trulzsch K, Sporleder T, Igwe E, Russmann H, Heesemann J . Contribution of the major secreted yops of Yersinia enterocolitica O:8 to pathogenicity in the mouse infection model. Infect Immun. 2004; 72(9):5227-34. PMC: 517446. DOI: 10.1128/IAI.72.9.5227-5234.2004. View

12.

Verbsky J, White A . Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol. 2004; 31(10):2071-5. View

13.

Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J . Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005; 201(9):1479-86. PMC: 2213182. DOI: 10.1084/jem.20050473. View

14.

Fitzgerald A, LeClercq S, Yan A, Homik J, Dinarello C . Rapid responses to anakinra in patients with refractory adult-onset Still's disease. Arthritis Rheum. 2005; 52(6):1794-803. DOI: 10.1002/art.21061. View

15.

Yu J, Wu J, Zhang Z, Datta P, Ibrahimi I, Taniguchi S . Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization. Cell Death Differ. 2005; 13(2):236-49. DOI: 10.1038/sj.cdd.4401734. View

16.

Johnston J, Barrett J, Nazarian S, Goodwin M, Ricciuto D, Ricuttio D . A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection. Immunity. 2005; 23(6):587-98. DOI: 10.1016/j.immuni.2005.10.003. View

17.

Fleischmann R, Tesser J, Schiff M, Schechtman J, Burmester G, Bennett R . Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis. 2006; 65(8):1006-12. PMC: 1798263. DOI: 10.1136/ard.2005.048371. View

18.

Boyden E, Dietrich W . Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet. 2006; 38(2):240-4. DOI: 10.1038/ng1724. View

19.

Franchi L, Amer A, Body-Malapel M, Kanneganti T, Ozoren N, Jagirdar R . Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Nat Immunol. 2006; 7(6):576-82. DOI: 10.1038/ni1346. View

20.

Miao E, Alpuche-Aranda C, Dors M, Clark A, Bader M, Miller S . Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat Immunol. 2006; 7(6):569-75. DOI: 10.1038/ni1344. View