Laboratory mice with a wild microbiota generate strong allergic immune responses.
Junjie MaEgon UrgardSolveig RungeCajsa Helena ClassonLaura MathäJulian M StarkLiqin ChengJaviera A ÁlvarezSilvia von ZedtwitzAusteja BaleviciuteSergio Martinez HoyerMuzhen LiAnne Marleen GernandLisa OsbeltAgata Anna BieleckaTill Robin LeskerHuey-Jy HuangSusanne VrtalaLouis BoonRudi BeyaertMikael AdnerItziar Martinez-GonzalezTill StrowigJuan DuSusanne NylénStephan P RosshartJonathan M CoquetPublished in: Science immunology (2023)
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 (T H 2) 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 T H 2 cell responses to incoming allergens, whereas preexisting T H 2 cells could also be recruited into the allergic immune response in a cytokine-driven 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.
Keyphrases
- immune response
- allergic rhinitis
- high fat diet induced
- air pollution
- microbial community
- induced apoptosis
- atopic dermatitis
- dendritic cells
- early life
- single cell
- escherichia coli
- oxidative stress
- stem cells
- regulatory t cells
- cell therapy
- wild type
- cell cycle arrest
- signaling pathway
- dna methylation
- cell proliferation
- insulin resistance
- gene expression
- heavy metals
- climate change
- human health
- genetic diversity