Journal article
The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection
R Alhallaf, Z Agha, CM Miller, AAB Robertson, J Sotillo, J Croese, MA Cooper, SL Masters, A Kupz, NC Smith, A Loukas, PR Giacomin
Cell Reports | CELL PRESS | Published : 2018
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 suppr..
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Awarded by GlaxoSmithKline
Funding Acknowledgements
This work was supported by the Australian National Health and Medical Research Council (NHMRC) grants 1037304 (to A.L.), 1099262 (to S.L.M.), 1086786 (to A.A.B.R. and M.A.C.), CJ Martin Fellowship 613718 (to P.R.G.), and Principal Research Fellowship 1020114 (to A.L.). We acknowledge funding support from the Iraqi Cultural Attache in Australia (to R.A.), the Queensland Department of Science, Information Technology and Innovation (to P.R.G.), the Sylvia and Charles Viertel Foundation (to S.L.M.), HHMI-Wellcome International Research Scholarship (to S.L.M.), Glaxosmithkline (to S.L.M.), as well as Development Grant (to P.R.G.) and scholarship (to Z.A.) support from AITHM. We thank Elizabeth Tynan (JCU) for critical reading of this manuscript.