Inflammasome-Independent Role for NLRP3 in Controlling Innate Antihelminth Immunity and Tissue Repair in the Lung

Alistair L Chenery, Rafid Alhallaf, Zainab Agha, Jesuthas Ajendra, James E Parkinson, Martha M Cooper, Brian H K Chan, Ramon M Eichenberger, Lindsay A Dent, Avril A B Robertson, Andreas Kupz, David Brough, Alex Loukas, Tara E Sutherland, Judith E Allen, Paul R Giacomin

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)2724-2734
Number of pages11
JournalJournal of Immunology
Issue number10
Early online date4 Nov 2019
Publication statusPublished - 15 Nov 2019

Bibliographical note

Copyright © 2019 The Authors.

Funding: This work was supported by the Wellcome Trust (106898/A/15/Z to J.E.A.), the Medical Research Council U.K. (MR/K01207X/1 [to J.E.A.] and MR/N003586/1 [to D.B.]), Australian National Health and Medical Research Council Grants 1117504 and 1132975 (to A.L.), the Queensland Department of Science, Information Technology and Innovation (to P.R.G.), and the Iraqi Cultural Attaché in Australia (to R.A.). T.E.S. was supported by Medical Research Foundation U.K. joint funding with Asthma U.K. (MRFAUK-2015-302).

Acknowledgement: We thank Vishva Dixit (Genentech) for the Nlrp3tm1Vmd mice. Thanks to Seth Masters (Walter and Eliza Hall Institute, Australia) for kindly providing B6-Nlrp3tm1Tsc/Siec and caspase-1/11 double-deficient mice. We thank the Flow Cytometry, Bioimaging, Genomic Technologies, and Biological Services core facilities at the University of Manchester.


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