Transient rewilding alters the lung immunologic landscape enhancing host protective responses to helminth infection 3007

Abstract Description Infection of laboratory-housed mice with the helminth N. brasiliensis (Nb) triggers lung inflammation, contributing to hemorrhaging and acute lung injury (ALI) followed by the development of a polarized type 2 pulmonary immune response and host protective macrophages. (Chen F et al, NI 2014, CR 2022). To examine whether exposure of mice to a rewilding environment might alter this response, mice were housed in an outdoor mesocosm reflecting a natural environment, for five weeks, after which they were returned to the lab and immediately infected with Nb. The RW mice showed a significantly lower worm burden at day 5 after infection. At day 2, increased ALI and lung hemorrhaging, was also significantly reduced.To examine potential changes in the lung immunologic landscape, scRNAseq was performed on rewilded WT and IL-4/IL-13-/- mice. RW WT mice showed significant increases in lung M2 macrophage activation, which was blocked in IL-4/IL-13-/- mice. Inoculation with microbiota isolated from RW mice, which includes Aspergillus species (Yeung F et al, CHM 2020), showed reduced worm burden, hemorrhaging and ALI after Nb infection. Inoculation with RW purified fungi A. fumigatus followed by Nb infection two weeks later showed similar host protective effects. These studies suggest that fungi acquired during transient rewilding can markedly alter pulmonary immune cell activation and function resulting in polarization towards type 2 inflammatory responses. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)