Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,095 bioRxiv papers from 295,270 authors.

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

By Alistair Chenery, Rafid Alhallaf, Z Agha, Jesuthas Ajendra, JE Parkinson, MM Cooper, BHK Chan, RM Eichenberger, Lindsay A Dent, Avril AB Robertson, Andreas Kupz, David Brough, Alex Loukas, Tara E Sutherland, Judith E Allen, PR Giacomin

Posted 13 Apr 2019
bioRxiv DOI: 10.1101/606392

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. While inflammasome proteins such as NLRP3 have important pro-inflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3-/- mice with N. brasiliensis. Unexpectedly, compared to 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 to WT mice. Notably, inflammasome activation was not evident early post-infection with N. brasiliensis and in contrast to Nlrp3-/- mice, anti-helminth responses were unaffected in caspase-1/11 deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 can constrain lung neutrophilia and helminth killing and negatively regulate type 2 immune responses in an inflammasome-independent manner.

Download data

  • Downloaded 454 times
  • Download rankings, all-time:
    • Site-wide: 23,629 out of 67,110
    • In immunology: 445 out of 1,706
  • Year to date:
    • Site-wide: 7,488 out of 67,110
  • Since beginning of last month:
    • Site-wide: 15,864 out of 67,110

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide

Sign up for the Rxivist weekly newsletter! (Click here for more details.)