Cryptococcus gattii infection dampens pulmonary inflammation by attenuating chemokine expression in the immunocompetent hosts (MPF6P.644)

Abstract Cryptococcal infections are caused mainly by two fungal species; Cryptococcus neoformans and C. gattii. While C. neoformansprimarily affects the immunocompromised hosts, C. gattii causes disease in immunocompetent individuals. Recent studies suggest that C. gattii is capable of infecting immunocompetent hosts because of its ability in dampening inflammatory cell recruitments. We hypothesizes that C. gattii dampens pulmonary inflammation by attenuating chemokine expression. Mice were infected with the highly virulent strains C. neoformansand C. gattii and then analyzed for kinetics of inflammatory cell infiltration and chemokine expression. Inflammatory cells and chemokine transcripts were found to be up-regulated and reached the peak levels at day 7 post-infection. Mice infected with C. gattii recruited much fewer myeloid dendritic cells, neutrophils, and CD4+ T helper cells into the lungs than those in C. neoformans-infected mice. Interestingly, the expression levels of Cxcl1, Cxcl2, Mcp1, Cxcl9,and Ip10transcripts known to be important for recruiting neutrophil and Th1 cells were significantly higher in C. neoformans-infected mice than in C. gattii-infected mice, whereas the expression levels of Ccl20, Ccl11 and Ccl17 were comparable. Our data suggest that C. gattii infection dampens pulmonary inflammation by down-regulating the pulmonary chemokine expression, thus resulting in the inability to mount protective immunity in immunocompetent hosts.