The NLRP3 inflammasome suppresses protective immunity to gastrointestinal helminth infection
Alhallaf, Rafid, Agha, Zainab, Miller, Catherine M., Robertson, Avril A.B., Sotillo-Gallego, Javier, Croese, John, Cooper, Matthew A., Masters, Seth L., Kupz, Andreas, Smith, Nicholas C., Loukas, Alex, and Giacomin, Paul R. (2018) The NLRP3 inflammasome suppresses protective immunity to gastrointestinal helminth infection. Cell Reports, 23 (4). pp. 1085-1098.
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Abstract
Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome. NLRP3-deficient mice displayed reduced pro-inflammatory type 1 cytokine responses and augmented protective type 2 immunity, which was reversed by IL-18 administration. NLRP3-dependent suppression of immunity partially required CD4+ cells but was apparent even in Rag1-/- mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections.
| Item ID: | 56690 |
|---|---|
| Item Type: | Article (Research - C1) |
| ISSN: | 2211-1247 |
| Copyright Information: | © 2018 The Author(s). Under Creative Commons Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). |
| Funders: | National Health and Medical Research Council (NHMRC), Iraqi Cultural Attache (ICA), Queensland Department of Science, Information Technology and Innovation (QDSITI), Sylvia and Charles Viertel Foundation (SCVF), Wellcome Trust (WT), GlaxoSmithKline (GSK), Australian Institute of Tropical Health and Medicine (AITHM) |
| Projects and Grants: | NHMRC 1037304, NHMRC 1099262, NHMRC 1086786, NHMRC CJ Martin Fellowship 613718, NHMRC Principal Research Fellowship 1020114 |
| Date Deposited: | 12 Feb 2019 00:03 |
| FoR Codes: | 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310799 Microbiology not elsewhere classified @ 33% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320499 Immunology not elsewhere classified @ 34% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320299 Clinical sciences not elsewhere classified @ 33% |
| SEO Codes: | 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50% 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 50% |
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