Towards a Humanized mouse model of Pneumocystis Pneumonia

Humanized NOG-EXL (huNOG-EXL) mice control P. murina infection significantly better than control NOG-EXL mice, as evidenced by markedly decrased lung fungal burdens at both 3 and 6 weeks post-infection. Human cytokine-generating CD4+ and CD8+ T cells in the lung and serum IgM antibody, which were specifically in responses to pneumocystis antigen, were detected in huNOG-EXL mice only. For humanized NOG-EXL mouse group at 6 weeks post-infection, the whole lung RNAseq analyses were performed and the data indicated that the lower lung fungal burden is associated with higher CD209 gene expression. Groups of humanized NOG-EXL and control NOG-EXL mice were infected with Pneumocystis murina. Three and six weeks post-infection, mouse lung fungal burden, cytokine-generating cells and serum antibody levels were measured. For humanized NOG-EXL group at 6 weeks post-infection, the whole lung RNAseq was analyzed.