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

13 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


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