A murine model of dual infection with cytomegalovirus and Pneumocystis carinii: Effects of virus-induced immunomodulation on disease progression

Abstract

Despite the use of antimicrobial prophylaxis, cytomegalovirus (CMV) and Pneumocystis carinii ( PC) pneumonia (PCP) are both leading causes of morbidity and mortality in immunocompromised patients. It has previously been reported that CMV infection modulates host immune responses with a variety of mechanisms which include the suppression of helper T cell functions and antigen presenting cell (APC) functions, both of which are critical for PCP resolution. However, the mechanisms of these interactions and other possible immune regulatory effects are not clearly understood. In this study, we investigated the impact of murine CMV (MCMV) induced immunomodulation on the progression of PCP in a co-infection model. Initial results show that dually infected mice had evidence of more severe PC disease, which include a greater loss of body weight, an excess lung PC burden and delayed clearance of PC from lungs, compared to mice with PC infection alone. At day 7 post-infection, dually infected mice had reduced numbers of MHC-II expressing cells in the lung interstitium and lymph nodes and reduced migration of CD11c + cells to both the tracheobronchial lymph nodes and alveolar spaces. Dual infected mice showed elevated numbers of specific CD8 responses concomitant with a decrease in activated CD4 + T cells in both the lymph nodes and in alveolar spaces when compared to mice infected with MCMV alone. These data suggest that MCMV infection inhibits the immune responses generated against PC which contribute to the delayed clearance of the organism.