AIDμS double knockout mice but not AID single knockout mice are highly susceptible to PneumocystisInfection

Abstract

Abstract Pneumocystispneumonia can be a life-threatening disease to individuals who are immunocompromised due to infection, such as HIV, receiving immunotherapy drugs including corticosteroids or due to genetic defect such as hyper IgM syndrome. B cells are important to the defense and clearance of Pneumocystisinfection; however, the exact role has yet to be elucidated. Prior studies have demonstrated that B cell antigen presentation and priming of CD4 +T cells plays a major role in Pneumocystisclearance, while passive transfer of immune serum can prevent Pneumocystisinfection in mice. To better understand the B cell role in control and clearance of Pneumocystisinfection, using a natural exposure model, we compared the kinetics of Pneumocystis murinainfection in activation-induced cytidine deaminase (AID −/−), AIDμS −/−double knockout, and wild-type C57BL/6 mice. By 5 – 6 weeks post initial exposure all three murine strains were infected with Pneumocystis murina, detected by qPCR of the single copy gene dihydrofolate reductase (DHFR). However, after 10 weeks of infection only the AIDμS −/−double knockout mice continued to have high levels of Pneumocystisinfection. These data suggests that deficiency of B cells to class switch, such as in the AID −/−strain, is not in itself enough to confer increased susceptibility to Pneumocystis. However, in combination with μS deficiency, which inhibits the secretion of antibodies, it is enough to debilitate the immune response resulting in uncontrolled Pneumocystisinfection. Intramural Research Program of the NIH Clinical Center