Inhibition of human endothelial cell chemokine production by the opportunistic fungal pathogen Cryptococcus neoformans

Cryptococcus neoformans is an encapsulated fungal pathogen commonly acquire d by inhalation, Extrapulmonary dissemination can lead to infection of the bloodstream and various organs, most commonly resulting in meningoencephali tis. However, infection with C. neoformans is often characterized by a scan t inflammatory response. The leukocyte response to infection depends in par t upon a gradient of chemotactic factors and adhesion molecules expressed b y the host vascular endothelium, yet the inflammatory response of human end othelial cells (EC) to C. neoformans has not been previously investigated. We found that incubation of primary human EC with C. neoformans did not ind uce chemokine synthesis, and resulted in differential inhibition of cytokin e-induced IL-8, IFN-gamma-inducible protein-10, and monocyte chemoattractan t protein-1. In contrast, C. neoformans had little effect on EC surface exp ression of the leukocyte ligand, ICAM-1, as determined by flow cytometry. M odulation of chemokine production was dependent on the chemokine under stud y, the inoculum of C. neoformans used, fungal viability, and cell-cell cont act, but independent of cryptococcal strain or encapsulation. These observa tions suggest a novel mechanism whereby C. neoformans can affect EC functio n and interfere with the host inflammatory response.