The NLRP3 inflammasome suppresses protective immunity to gastrointestinal helminth infection

Journal Publication ResearchOnline@JCU
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;Giacomin, Paul R.
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.

Journal

Cell Reports

Publication Name

N/A

Volume

23

ISBN/ISSN

2211-1247

Edition

N/A

Issue

4

Pages Count

N/A

Location

N/A

Publisher

Elsevier

Publisher Url

N/A

Publisher Location

N/A

Publish Date

N/A

Url

N/A

Date

N/A

EISSN

N/A

DOI

10.1016/j.celrep.2018.03.097