Independent Research Scholar NIAID, NIH Bethesda, Maryland, United States
Introduction/Rationale: Genetics and Environmental factors including an individual’s microbial experience, infection history and tissue specific factors are important drivers of immune variation and susceptibility to infections. However, how these factors interact to contribute to immune variation is not well understood.
Methods: Here, we show results using various inbred strains of mice - C57BL/6, B10.BR-H2k2 H2-T18a/SgSnJJrep (B10.BR) and BalbC, to understand the contributions of genetics, environmental factors and infection history to heterogenicities in the myeloid cell composition within the lungs and its effect on subsequent infections. For assessing the contribution of an environmental factor to immune variation, we used the rewilding model, a process of exposing mice to the outdoor enclosure while for infection, we used a helminth infection model, Nippostrongylus brasiliensis.
Results: Our results demonstrate that following rewilding, the B10.BR mice showed increased monocytic infiltration compared to the C57BL/6 inbred mouse that is accompanied by increased myelopoiesis in the B10.BR strain of mice. Further analysis shows that both strains of mice have an increased proportions of Ly6chi inflammatory monocytes following rewilding. Similarly, during an exuberant Type 2 inflammation induced by exposure of three different inbred mice strains, C57BL/6, BalbC and B10.BR mice, to lung-migrating helminth, Nippostrongylus brasiliensis (Nb), the B10.BR and the C57BL/6 strain of mice, have accelerated alternatively activated macrophage phenotype compared to the other inbred strain of mice examined both at day 7 and at day 28 post Nb exposure. Interestingly, we observed that that this difference also has consequences on strain dependent parasite clearance and helminth mediated influenza control.
Conclusion: Together, these results suggest that genetic and environmental factors combine to drive variation in myeloid cell composition within the airway mucosa that have consequences to subsequent infection outcomes.
