ABSTRACT
BACKGROUND: Being born and raised in a farm provides a long-lasting protection for allergies. The microbial environment provided by farm animals is crucial to induce this protective effect, although underlying immune mechanisms remain elusive. OBJECTIVE: To establish a mouse model of global exposure to the farming environment and to study immunologic changes linked to protection of allergy. METHODS: Mice colonies were bred in parallel in a farm cowshed and the university animal facility (AF). Mice from both locations were subjected to a skin contact allergy model. Peripheral blood cells and cell cytokine production were assessed in both populations. In addition, the gut microbiome at various ages was characterized. RESULTS: Mice born in the farm were less prone to develop allergy than mice bred in the AF. Mice transfers between the AF and the farm showed a better protection when mice were moved to the farm early in life. As compared to AF-bred mice, farm mice displayed early immune activation with higher CD4+ T cell population, in particular CD4+ CD25+ FoxP3- (activated cells). The cytokine profile of mice from the farm was skewed towards an IL-17 and IL-22 secreting cell profile accompanied by increased IL-10 secretion. These differences were mostly seen within a specific age window between birth and 8 weeks of age. Microbiome analysis showed differences between 4 and 20 weeks old mice and between farm and AF mice with an increased number of Murine mastadenovirus B in young farm mice exclusively. CONCLUSION: The farming environment provides a strong, allergy protective IL-22 stimulus and generates activated CD4+ T cells. Exposure to the farm environment early in their life may also provide a better protection for contact skin allergy. Whether a viral trigger might decisively influence protection for allergies remains to be determined.
