BioProject

The immunology of asthma is complex and involves the loss of immunoregulatory pathways with the adoption of a Western lifestyle inducing changes in the diversity and the time exposure to microorganisms. More...

The immunology of asthma is complex and involves the loss of immunoregulatory pathways with the adoption of a Western lifestyle inducing changes in the diversity and the time exposure to microorganisms. Gammaherpesviruses (γHVs) are among the most prevalent human viruses. Establishing early life infection, they profoundly imprint the immune system of their hosts. Using Murid herpesvirus 4 (MuHV-4), a mouse model of human γHV infections, we showed that both lung resident and bone marrow-derived group 2 innate lymphoid cells (ILC2s) displayed lasting reduced capacity to expand and to produce type 2 cytokines, in response to house dust mites, in an IFN-γ depend manner. Importantly, we uncovered that pulmonary ILC2s represent essential niche cells that imprint alveolar macrophage tissue-specific identity upon monocyte replenishment in infection settings. In particular, we showed that MuHV-4 infection disrupts the normal ILC2-epithelial cells circuit that imprints monocytes-derived AMs for type 2 functions without affecting their differentiation. These results reveal that persistent γHV infection shapes the alveolar landscape much beyond the initial acute infection through long-term effect on ILC2 niche cells. Overall design: Cells from lungs of non-infected and MuHV-4 infected mice subjected to different doses of HDM (0, 1, 3) were collected. Less...