Studies of receptors and mechanisms of cell signaling involved in cytokine secretion by epithelial cells during interaction with Histoplasma capsulatum

Abstract

Several studies about interaction between pathogenic fungi and the host cell are performed using macrophages, dendritic cells or neutrophils. There are few studies about interaction between Histoplasma capsulatum and epithelial cells. Epithelial cells act as a structural barrier against inhaled particles such as microorganisms, pollutants, and allergens. In addition, these cells produce inflammatory mediators such as cytokines, chemokines, and pattern recognition receptors and thus may contribute to the innate immune defense. Therefore, studies about cellular and molecular mechanisms involved in the interaction between human epithelial cells and pathogens are essential.The objectives of this project are to analyze, during the interaction with H. capsulatum: (i) the expression of TLRs ("Toll-like receptors") and PARs ("protease-activated receptors") in epithelial cells, (ii) the modulation of cell signaling pathways, as activation of SFKs ("Src-family kinases"), MAPKs ("mitogen-activated protein kinases") and NF-kB ("nuclear factor-kB"), and whether these proteins are involved in cytokine secretion (IL-6, IL-8 and IL-10) during H. capsulatum-epithelial cell interaction, (iii) the importance of TLRs in PAR expression, (iv) whether factors secreted by H. capsulatum promote activation of SFKs, MAPKs, NF-kB and cytokine secretion, and (v) which components of the fungal cell wall induce the expression of TLRs and PARs and cytokine secretion by epithelial cells.