Resumo

Histoplasmosis is a systemic human mycosis caused by the dimorphic fungus Histoplasma capsulatum. Infection occurs by inhaling conidia and mycelial fragments with subsequent conversion to pathogenic yeast forms in host lungs. Pulmonary epithelial cells represent the first line of defense against inhaled particles or microorganisms. These cells contribute to pulmonary mucosal immunity by producing inflammatory mediators, such as cytokines and chemokines, and by the expression of pattern recognition receptors. Therefore, studies about cellular and molecular mechanisms involved in the interaction between human epithelial cells and H. capsulatum may contribute to understand the role of these cells in modulation of host immune response. In this study, we demonstrate that H. capsulatum yeasts induce inflammatory cytokines secretion by the human lung epithelial cells A549. A549 cells were incubated with live or formaldehyde-fixed H. capsulatum yeasts for different periods of time (5-48 h), and concentrations of IL-6, IL-8 and IL-10 in these culture supernatants were analyzed using Sandwich ELISA kits. It was verified that live and formaldehyde-fixed yeasts were able to increase IL-6 and IL-8 secretion by A549 cells. However, IL-10 was undetectable in these cultures. In addition, to evaluate whether components released by H. capsulatum are able to promote cytokine secretion, A549 cells were incubated with conditioned medium of this fungus or live yeasts in a transwell system. It was observed that both conditioned medium and live yeasts in the upper compartment promoted increase of IL-6 and IL-8 levels in culture supernatants when compared to basal levels. Taking together, these results indicate that both H. capsulatum yeasts and secreted factors by this fungus are able to induce inflammatory cytokine secretion by A549 cells, suggesting that pulmonary epithelial cells may participate in early host immune response in this fungal infection. Epithelial cell receptors and cell signaling pathways involved in this process are under investigation in our laboratory. Supported by FAPESP, CNPq and CAPES.