Cell-mediated immunity in host resistance against infection caused by Penicillium marneffei

Penicillium marneffei is one of the most important opportunistic infectious pathogens in AIDS patients in Thailand and Southeast Asia. However, very little is known about the host defence mechanisms against P. marneffei infection. In the present study, we established the first experimental murine model of chronic pulmonary and disseminated infection using P. marneffei, and examined the immunological response to such infection in euthymic and athymic mice. In this model, micro-organisms inoculated intratracheally multiplied progressively in the lungs and disseminated to the liver and spleen. However, the number of organisms decreased gradually in these organs. In contrast, congenitally athymic mice developed severe pulmonary and disseminated systemic mycosis. Pulmonary penicilliosis marneffei was associated with a marked cellular inflammatory response as evident by histological abnormalities and increased intraparenchymal leucocyte count. To confirm the importance of cell-mediated immunity in host resistance to P. marneffei infection, we transferred nylon wool non-adherent spleen cells into the athymic mice. Such treatment significantly reduced the number of yeasts in the organs of athymic mice. Taken together, our results demonstrate that the cell-mediated immunity play a central role in a host defence mechanism against infection with P. marneffei, and suggest that our new model may be a useful approach for studying the pathogenesis of this fungal disease.