Late Breaking Abstract - Role of PD-1/PD-L1 pathway in Pneumocystis pneumonia

Abstract

Pneumocystis: is an unusual, fascinating, opportunistic fungal pathogen, which often causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Though it has been found for more than 100 years, the immune mechanism remains unclear. The inhibitory receptor programmed death 1 (PD-1), a negative regulator of activated T cells, has been reported to have effect on tumor escape, immune tolerance and infectious disease. In this study, we examined the role of PD-1/PD-L1 pathway in PCP patients and mice. Flow cytometry and Real-Time PCR were used to detect the expression of PD-1/PD-L1 in PCP patients and mice. The affection of PD-1 deficiency was carefully demonstrated through WT and PD-1^-/- mice models. The interaction between PD-1 positive macrophages and T cells was also determined. Our data showed that Pneumocytsis infection unregulated the PD-1/PD-L1 expression; PD-1 deficiency helped hosts to clear Pneumocystis organism by enhancing the phagocytic function of macrophages and pulmonary Th1/Th17 response. Additionally, the high PD-L1 expression on macrophage may contribute little to T cell suppression. Taken together, our data demonstrated that PD-1/PD-L1 pathway played role in the regulation of innate and adaptive immune response and suggested that manipulation of this pathway might be a strategy of immunotherapy for some PCP patients.