AbstractBackgroundCryptococcus neoformans(C. neoformans) is a globally distributed fungal pathogen with the potential to cause serious disease, particularly among immune compromised hosts. Exposure to this organism is believed to occur by inhalation and may result in pneumonia and/or disseminated infection of the brain as well as other organs. Little is known about the role of airway epithelial cells in cryptococcal recognition or their ability to induce an inflammatory response.MethodsImmortalized BEAS-2B bronchial epithelial cells and primary normal human bronchial epithelium (NHBE) were stimulatedin vitrowith encapsulated or acapsularC. neoformanscultivated at room temperature or 37°C. Activation of bronchial epithelial cells was characterized by analysis of inflammatory cytokine and chemokine expression, transcription factor activation, fungal-host cell association, and host cell damage.ResultsViableC. neoformansis a strong activator of BEAS-2B cells, resulting in the production of the neutrophil chemokine Interleukin (IL)-8 in a time- and dose-dependent manner. IL-8 production was observed only in response to acapsularC. neoformansthat was grown at 37°C.C. neoformanswas also able to induce the expression of the chemokine CXCL1 and the transcription factor CAAT/enhancer-binding protein beta (CEBP/β) in BEAS-2B cells. NHBE was highly responsive to stimulation withC. neoformans; in addition to transcriptional up regulation of CXCL1, these primary cells exhibited the greatest IL-8 secretion and cell damage in response to stimulation with an acapsular strain ofC. neoformans.ConclusionThis study demonstrates that human bronchial epithelial cells mediate an acute inflammatory response toC. neoformansand are susceptible to damage by this fungal pathogen. The presence of capsular polysaccharide andin vitrofungal culture conditions modulate the host inflammatory response toC. neoformans. Human bronchial epithelial cells are likely to contribute to the initial stages of pulmonary host defensein vivo.