The NLRP3 inflammasome suppresses protective immunity to gastrointestinal helminth infection
- Author(s)
- Alhallaf, R; Agha, Z; Miller, CM; Robertson, AAB; Sotillo, J; Croese, J; Cooper, MA; Masters, SL; Kupz, A; Smith, NC; Loukas, A; Giacomin, PR;
- Details
- Publication Year 2018-04-24,Volume 23,Issue #4,Page 1085-1098
- Journal Title
- Cell Reports
- Publication Type
- Journal Article
- Abstract
- Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1beta. 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.
- Publisher
- Cell Press
- Research Division(s)
- Inflammation
- PubMed ID
- 29694887
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2018.03.097
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2018.03.097- NHMRC Grants
- NHMRC/1099262,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-05-18 09:33:20
Last Modified: 2018-06-27 09:43:32