Physiological microbial exposure transiently inhibits mouse lung ILC2 responses to allergens

Katharine E. Block, Koji Iijima, Mark J. Pierson, Daniel A. Walsh, Rinna Tei, Tamara A. Kucaba, Julie Xu, Mohammad Haneef Khan, Christopher Staley, Thomas S. Griffith, Henry J. McSorley, Hirohito Kita, Stephen C. Jameson

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Lung group 2 innate lymphoid cells (ILC2s) control the nature of immune responses to airway allergens. Some microbial products, including those that stimulate interferons, block ILC2 activation, but whether this occurs after natural infections or causes durable ILC2 inhibition is unclear. In the present study, we cohoused laboratory and pet store mice as a model of physiological microbial exposure. Laboratory mice cohoused for 2 weeks had impaired ILC2 responses and reduced lung eosinophilia to intranasal allergens, whereas these responses were restored in mice cohoused for ≥2 months. ILC2 inhibition at 2 weeks correlated with increased interferon receptor signaling, which waned by 2 months of cohousing. Reinduction of interferons in 2-month cohoused mice blocked ILC2 activation. These findings suggest that ILC2s respond dynamically to environmental cues and that microbial exposures do not control long-term desensitization of innate type 2 responses to allergens.

Original languageEnglish (US)
Pages (from-to)1703-1713
Number of pages11
JournalNature immunology
Volume23
Issue number12
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
We thank UMN Flow Cytometry Resource Facility, CFI Dirty Mouse Colony, UMN BSL-3 Program, Minnesota Supercomputing Institute, Cytokine Reference Laboratory and UMN Research Animal Resources for support. We thank Jamequist and Kita lab members for thoughtful discussion. This work was supported by the NIH (grant nos. R01HL117823 to H.K., T32HL007741 to K.E.B. and R35GM140881 to T.S.G.), Minnesota Partnership for Biotechnology and Medical Genomics (grant no. 16.48 to S.C.J. and H.K.) and UMN Medical School (grant no. AIRP-CP-21 to S.C.J.).

Funding Information:
We thank UMN Flow Cytometry Resource Facility, CFI Dirty Mouse Colony, UMN BSL-3 Program, Minnesota Supercomputing Institute, Cytokine Reference Laboratory and UMN Research Animal Resources for support. We thank Jamequist and Kita lab members for thoughtful discussion. This work was supported by the NIH (grant nos. R01HL117823 to H.K., T32HL007741 to K.E.B. and R35GM140881 to T.S.G.), Minnesota Partnership for Biotechnology and Medical Genomics (grant no. 16.48 to S.C.J. and H.K.) and UMN Medical School (grant no. AIRP-CP-21 to S.C.J.).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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