Involvement of toll-like receptor, integrins and their respective cell signaling pathways in cytokine secretion by epithelial cells during infection with Paracoccidioides brasiliensis

Abstract

Paracoccidioidomycosis is caused by the fungal pathogen of the genus Paracoccidioides and is the most prevalent systemic mycosis in Latin America. About 80% of the cases occur in Brazil. And, due to the increasing number of cases of this mycosis in our country, studies about interactions between these fungi and host are essential to understand the events involved in the establishment of infection and spread of pathogen.Epithelial cells are the first contact site for pathogens. Besides forming a physical barrier against particles, these cells contribute to the host innate immune system to produce inflammatory mediators, such as cytokines. Thus, the interaction of pathogens with host cell receptors, such as integrins and Toll-like Receptors, can lead to recruitment of these molecules to domains in the plasma membrane, named membrane rafts, causing activation of the receptors and their respective cell signaling pathways, culminating in cytokine expression.Thus, the main objective of this project is to study the cellular mechanisms involved in secretion of cytokines by epithelial cells infected with P. brasiliensis. For this, during infection with P. brasiliensis yeasts, we will study the: (i) expression of integrins (alpha 3 and alpha 5) and TLRs (TLR2 and TLR4), (ii) interaction between receptors, (iii) recruitment of receptors to membrane rafts of epithelial cells, (iv) importance of each receptor in secretion of IL-6 and IL-8, and (v) activation and modulation of TLR signaling pathways and SFKs in IL-6 and IL-8 secretion.