Experimental Pneumocystis infection in dexamethasone immunosuppressed macaques

To establish an experimental model of Pneumocystis jirovecii pneumonia (PJP) in the context of drug-induced immunosuppression, cohorts of macaques were chronically treated with dexamethasone and subsequently exposed to natural transmission of Pneumocystis through co-housing with other Pneumocystis colonized or infected 'seeder' macaques. Through flow cytometry, we observed that long-term dexamethasone treatment reproducibly reduced the frequency and cell numbers of CD4 T cells in the peripheral blood and bronchoalveolar lavage (BAL) in both Japanese (Macaca fuscata) and rhesus macaques (Macaca mulatta), reflective of a state of chronic immunosuppression. This was accompanied by a reduction in the frequency and cell number of CD20 + B cells and the absence of antibody responses against the protective Pneumocystis antigen KEX1 in the peripheral blood. Pneumocystis-specific polymerase chain reaction and histologic evidence of Pneumocystis infection in serial BAL samples demonstrated that dexamethasone induced immunosuppression rendered both Japanese and rhesus macaques susceptible to persistent Pneumocystis colonization and subsequent infection. Moreover, disease progression was associated with increased neutrophil infiltration in the lung. Insight gained from this model will aid the development of novel prevention and treatment strategies in a highly relevant model of Pneumocystis infection.