PhD student Michigan Medicine, University of Michigan Ann Arbor, Michigan, United States
Disclosure(s):
Sophia Maxfield: No financial relationships to disclose
Introduction/Rationale: Countries with frequent exposure to respiratory pathobionts report lower incidence of asthma. Despite its implications for global health, unequivocal evidence for- and careful dissection of- a protective mechanism remains scant. Here, we sought to determine if and how microbial experience may alter development of asthma.
Methods: Using a common human airway colonizing bacteria Streptococcus pneumoniae (Spn), we modeled repeated microbial inhalations experienced by humans, and utilized the common human aeroallergen house dust mites (HDM) to model allergen-induced allergic airway eosinophilia.
Results: Consistently, naive C57BL/6J mice developed allergic airway eosinophilia following HDM challenge, while their Spn-experienced counterparts did not. Protection by Spn experience was irrespective of atopy, as genetically susceptible FVB/NJ mice were also protected. Transcriptional analysis demonstrated that Spn experience-induced protection was characterized by lower type 2 cytokine production and subsequent reductions in epithelial-derived eotaxins during HDM encounter. This was accompanied by reduced ILC2s, HDM-specific Th2 cells, cDC2s, and eosinophils, and significantly increased cDC1s and Tregs. Using mice lacking IFN-γ, IL-17, or IL-22, we next evaluated necessity of Spn-induced type 1 and type 3 effector T cells in anti-allergic protection and found no compromise in antiallergic protection. Instead, preliminary data suggest a role for IL-10 in this protection.
Conclusion: Our findings suggest that frequent exposure to respiratory pathobionts may indeed protect against development of allergic airway eosinophilia. Ongoing studies are focused on dissecting the cellular and molecular mechanisms driving this microbe-induced antiallergic protection.
