B-Cell Responses in the Lung during Acute Pneumocystis Infection

Abstract

Abstract Pneumocystis jiroveci is an opportunistic fungal organism that causes Pneumocystis pneumonia in humans with HIV-AIDS or in other immunocompromised individuals. A unique aspect of Pneumocystis is although it is associated with T cell immunodeficiency, recent evidence shows that B cells play a key role as antigen presenting cells in the lung to prime fungal T cell responses (Lund et.al, 2006; Lund et.al, 2003; and Opata et.al, 2015). Our lab has used the murine model of Pneumocystis as many mutations that predispose to Pneumocystis infections in humans replicate in this model (Elsegeiny et al. 2018). In contrast to other infections where dendritic cells are critical antigen presentation cells (APCs), it has been shown that in the context of Pneumocystis, B cells are the key APCs. Our lab has previously shown that IgM−/− mice have delayed CD4+ T cell priming as well as delayed fungal clearance. Therefore we hypothesize that germline encoded B cells react to specific Pneumocystis antigens, and that these B cells are critical to prime Pneumocystis specific CD4+ T cells. We have found that both C57BI/6 and Aicda−/− mice have anti-Pneumocystis IgM prior to infection. Moreover, we found anti-Pneumocystis antibodies in human cord blood and using proteomics we have identified that cord blood pulled down several antigens including PNEG_01454. In the murine model, we found that IgM reacts with a fungal protein involved in ascospore assembly, Meu10. Additionally, using recombinant Meu10 we found Meu10 specific IgM B cells in spleen by Elispot. Current studies are assessing if Meu10 is a T cell epitope and whether Meu10 specific B cells facilitate T cell mediated clearance of the fungus in vivo.