Fatal Disseminated Cryptococcus gattii Infection in New Mexico

We report a case of fatal disseminated infection with Cryptococcus gattii in a patient from New Mexico. The patient had no history of recent travel to known C. gattii-endemic areas. Multilocus sequence typing revealed that the isolate belonged to the major molecular type VGIII. Virulence studies in a mouse pulmonary model of infection demonstrated that the strain was less virulent than other C. gattii strains. This represents the first documented case of C. gattii likely acquired in New Mexico

Cryptococcus neoformans induces IL-8 secretion and CXCL1 expression by human bronchial epithelial cells

<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>(<it>C. neoformans</it>) 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.</p> <p>Methods</p> <p>Immortalized BEAS-2B bronchial epithelial cells and primary normal human bronchial epithelium (NHBE) were stimulated <it>in vitro </it>with encapsulated or acapsular <it>C. neoformans </it>cultivated 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.</p> <p>Results</p> <p>Viable <it>C. neoformans </it>is 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 acapsular <it>C. neoformans </it>that was grown at 37°C. <it>C. neoformans </it>was 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 with <it>C. neoformans</it>; 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 of <it>C. neoformans</it>.</p> <p>Conclusion</p> <p>This study demonstrates that human bronchial epithelial cells mediate an acute inflammatory response to <it>C. neoformans </it>and are susceptible to damage by this fungal pathogen. The presence of capsular polysaccharide and <it>in vitro </it>fungal culture conditions modulate the host inflammatory response to <it>C. neoformans</it>. Human bronchial epithelial cells are likely to contribute to the initial stages of pulmonary host defense <it>in vivo</it>.</p

T-cell Subsets and Antifungal Host Defenses

It has been long appreciated that protective immunity against fungal pathogens is dependent on activation of cellular adaptive immune responses represented by T lymphocytes. The T-helper (Th)1/Th2 paradigm has proven to be essential for the understanding of protective adaptive host responses. Studies that have examined the significance of regulatory T cells in fungal infection, and the recent discovery of a new T-helper subset called Th17 have provided crucial information for understanding the complementary roles played by the various T-helper lymphocytes in systemic versus mucosal antifungal host defense. This review provides an overview of the role of the various T-cell subsets during fungal infections and the reciprocal regulation between the T-cell subsets contributing to the tailored host response against fungal pathogens