Laboratory mice with a wild microbiota generate strong allergic immune responses

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  • Junjie Ma
  • Solveig Runge
  • Cajsa H. Classon
  • Laura Mathä
  • Julian M. Stark
  • Liqin Cheng
  • Javiera A. Álvarez
  • Silvia von Zedtwitz
  • Austeja Baleviciute
  • Sergio Martinez Hoyer
  • Muzhen Li
  • Anne Marleen Gernand
  • Lisa Osbelt
  • Agata Anna Bielecka
  • Till R. Lesker
  • Huey Jy Huang
  • Susanne Vrtala
  • Louis Boon
  • Rudi Beyaert
  • Mikael Adner
  • Itziar Martinez Gonzalez
  • Till Strowig
  • Juan Du
  • Susanne Nylén
  • Stephan P. Rosshart

Allergic disorders are caused by a combination of hereditary and environmental factors. The hygiene hypothesis postulates that early-life microbial exposures impede the development of subsequent allergic disease. Recently developed "wildling"mice are genetically identical to standard laboratory specific pathogen-free (SPF) mice but are housed under seminatural conditions and have rich microbial exposures from birth. Thus, by comparing conventional SPF mice with wildlings, we can uncouple the impact of lifelong microbial exposures from genetic factors on the allergic immune response. We found that wildlings developed larger populations of antigen-experienced T cells than conventional SPF mice, which included interleukin-10-producing CD4 T cells specific for commensal Lactobacilli strains and allergy-promoting T helper 2 (TH2) cells. In models of airway exposure to house dust mite (HDM), recombinant interleukin-33, or Alternaria alternata, wildlings developed strong allergic inflammation, characterized by eosinophil recruitment, goblet cell metaplasia, and antigen-specific immunoglobulin G1 (IgG1) and IgE responses. Wildlings developed robust de novo TH2 cell responses to incoming allergens, whereas preexisting TH2 cells could also be recruited into the allergic immune response in a cytokinedriven and TCR-independent fashion. Thus, wildling mice, which experience diverse and lifelong microbial exposures, were not protected from developing pathological allergic immune responses. Instead, wildlings mounted robust allergic responses to incoming allergens, shedding new light on the hygiene hypothesis.

Original languageEnglish
Article numberadf7702
JournalScience immunology
Volume8
Issue number87
Pages (from-to)1-16
ISSN0065-2776
DOIs
Publication statusPublished - 2023

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