Microbiota acquisition during early life drives the development of the immune system. The composition and diversity of the aquired microbiome can dictate susceptibility to many diseases, including: diabetes, asthma, and perhaps pneumonia.
Some studies have suggested that commensal intestinal bacteria may mediate pulmonary immunity, proposing a gut-brain axis. Mechanistically, however this crosstalk has not yet been described.
Gray et al. demonstrate that early life (maternal) antibiotic exposure results in increased susceptibility to pneumonia by compromising pulmonary IL-22 production.
ILC3s were identified as the main producers of IL-22 in the lungs. Early antibiotic exposure permanently disrupted the infiltration of IL-22+ILC3s into the lungs of mice and human newborns.
Interactions between the microbiota and intestinal CD103+ CD11b+ DCs drove the expression of CCR4 on ILC3s in a CCL17 dependent manner. ILC3s from mice treated with antibiotics as neonates did not express CCR4, resulting in their intrinsic homing defect.
In these studies, early life antibiotic treatment significantly depleted the intestinal microbiota, but did not have a major effect on the lung microbiota. Therefore, the authors suggest that antibiotic depletion of the intestinal microbiota modulated pulmonary immunity. However, it is possible that commensal organisms and CD103+CD11b+ DCs from the skin may be playing playing a role.
None the less, this study demonstrated that microbiota acquisition during early life drives pulmonary accumulation of IL-22+ILC3s that are protective against pneumonia.
I would like to know whether neonatal antibiotics exposure effects the infiltration of other cells, such as regulatory T cells or IgA-expressing plasma cells, into the lung.