Inflammasome-independent role for NLRP3 in controlling innate antihelminth immunity and tissue repair in the lung

Chenery, Alistair L., Alhallaf, Rafid, Agha, Zainab, Ajendra, Jesuthas, Parkinson, James E., Cooper, Martha M., Chan, Brian H. K., Eichenberger, Ramon M., Dent, Lindsay A., Robertson, Avril A. B., Kupz, Andreas, Brough, David, Loukas, Alex, Sutherland, Tara E., Allen, Judith E., and Giacomin, Paul R. (2019) Inflammasome-independent role for NLRP3 in controlling innate antihelminth immunity and tissue repair in the lung. Journal of Immunology, 203 (10). 1900640. pp. 2724-2734.

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Alternatively activated macrophages are essential effector cells during type 2 immunity and tissue repair following helminth infections. We previously showed that Ym1, an alternative activation marker, can drive innate IL-1R-dependent neutrophil recruitment during infection with the lung-migrating nematode, Nippostrongylus brasiliensis, suggesting a potential role for the inflammasome in the IL-1-mediated innate response to infection. Although inflammasome proteins such as NLRP3 have important proinflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3 -/- mice with N. brasiliensis Unexpectedly, compared with wild-type (WT) mice, infected Nlrp3 -/- mice had increased neutrophilia and eosinophilia, correlating with enhanced worm killing but at the expense of increased tissue damage and delayed lung repair. Transcriptional profiling showed that infected Nlrp3 -/- mice exhibited elevated type 2 gene expression compared with WT mice. Notably, inflammasome activation was not evident early postinfection with N. brasiliensis, and in contrast to Nlrp3 -/- mice, antihelminth responses were unaffected in caspase-1/11-deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 has a role in constraining lung neutrophilia, helminth killing, and type 2 immune responses in an inflammasome-independent manner.

Item ID: 60631
Item Type: Article (Research - C1)
ISSN: 1550-6606
Copyright Information: Copyright © 2019 The Authors. This article is Open Access under the terms of a Creative Commons Attribution (CC BY 4.0) international license.
Funders: Wellcome Trust (WT), Medical Research Council, UK, National Health and Medical Research Council (NHMRC), Queensland Department of Science, Information Technology and Innovation (QDSITI), Iraqi Cultural Attache (ICA), Asthma UK
Projects and Grants: NHMRC 1117504 and 1132975
Date Deposited: 21 Nov 2019 06:56
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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