LAUSR

remains unclear due to the lack of culture methods and simple murine models of PCP. We have found that PCP spontaneously developed in mice lacking Caspase 8 and Ripk3 (DKO), both of these genes are essential for death ligandinduced apoptosis and programmed necrosis, respectively. Methods: The DKO mice were used to analyze the mechanism underlying the development of PCP. Results and Conclusions: DKO mice developed lymphadenopathy with an aberrant accumulation of CD3B220 lymphocytes. Of note, DKO mice spontaneously developed severe pneumonia where the alveoli were filled with a large number of organisms, similar to the findings of HIV-PCP. RNA sequencing and qPCR analysis showed that the expression of exhaustion markers such as PD-1, PD-L1, and PDL2 was markedly upregulated in the lungs of infected DKO mice compared to wild-type or uninfected DKO mice. FACS analysis showed that PD-1 was upregulated in both CD4 and CD8 T lymphocytes. These results suggest that a defect in acquired immunity and elevation of exhaustion markers might constitute a niche for expansion of P. murina in the lungs of DKO mice. Since elevated PD-1 expression in lymphocytes has been reported in HIV patients, this murine model may mimic the pathophysiology of PCP in HIV patients.