The role of CD4+ T cell subsets in the clearance of Pneumocystis murina pneumonia in mice (MPF6P.734)

Abstract Pneumocystis (PC) Pneumonia remains a serious complication in the immuno-compromised host. The host defense against PC is critically dependent upon CD4+ T cells. The role of specific T-cell subsets that mediate host resistance against PC infection remains unclear. We use STAT transcription factor knockout (KO) mice to determine the role of Th1, Th2, and Th17 cells in PC infection. After 28 days infection with PC, serum, lung tissue, and mediastinal lymph node (LN) were collected. LN and lung tissue cells were measured for cytokines by ELISpot and intracellular staining. Total lung RNA was measured for PC burden by RT-qPCR. Cytokines were assayed from cell culture supernatant. Anti-PC antibody was measured by ELISA.Stat4, Stat6 single KO, and Stat4/6 double KO mice all were resistant to PC compared to the Rag2/gc KO mice. Stat4 was required for a Th1 response and Stat6 was required for a Th2 response. STAT3fl/fl/CD4Cre+ mice had partial susceptibility of PC. Stat3 expression was required in CD4+ T cells for PC specific Th17 responses. STAT4/6 double KO crossed to STAT3fl/fl/CD4Cre+ (Triple KO) mice were highly susceptible to PC infection compare to single and double KO mice. Individual Stat4 and 6 and double mutants clear PC. STAT3fl/fl/CD4Cre+ conferred partial susceptibility to PC. Triple KO were as susceptible for PC as Rag2/gc KO mice. These data support the hypothesis that PC is a true opportunist and that various T-cell subsets can confer protection against infection.