There is a high probability that this interaction is indirect, because yeasts are able to bind to murine laminin that is recognized by 31 integrin (McMahon et al., 1995; Kikkawa et al., 1998; Tagliari et al., 2012). cells by interacting with 3 and 5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation. var. and var. that are etiological agents of the classical and the African histoplasmoses, respectively. Classical histoplasmosis is widely distributed in Papain Inhibitor the Americas. In the United States, highly endemic areas include the Mississippi and Ohio River valleys. This mycosis also occurs in countries of Central and South America, and in Brazil, outbreaks of histoplasmosis have been reported after exposure to fragments (Martins et al., 2003; Guimar?es et al., 2006; Oliveira et al., 2006; Rocha-Silva et SCA14 al., 2014). is a thermally dimorphic fungus, which is found in soil, caves, and abandoned constructions that are enriched in bat or bird excrements (Smith and Kauffman, 2012). Infection with occurs by inhaling microconidia or mycelial fragments Papain Inhibitor which then settle in the hosts lungs and convert to yeast forms (Mihu and Nosanchuk, 2012). Some fungi are internalized by phagocytes and Papain Inhibitor are able to survive and multiply within macrophages, allowing, in this manner, dissemination of to several organs through the bloodstream or lymphatic system (Mihu and Nosanchuk, 2012; Adenis et al., 2014). The severity of this mycosis depends on the number of inhaled fungal particles and the immune status of the host. In immunocompetent individuals, a small inoculum can cause asymptomatic infection or acute pulmonary histoplasmosis. Individuals with pre-existing lung diseases, such as emphysema, may develop chronic pulmonary histoplasmosis, and immunocompromised patients may present disseminated histoplasmosis (Smith and Kauffman, 2012). Histoplasmosis is responsible for low rates of morbidity and mortality among immunocompetent patients. However, among immunocompromised patients, morbidity, and Papain Inhibitor mortality of this mycosis have increased mostly due to HIV (Adenis et al., 2014). Histoplasmosis is an AIDS-defining illness, and some authors consider HIV-associated histoplasmosis a neglected disease in South America. Unhappily, these cases are often confused with tuberculosis or pneumocystosis (Nacher et al., 2013). In Brazil, in the state of Cear, a study of a 4-years period (2006C2010) reported 208 cases of histoplasmosis in HIV-positive patients. Histoplasmosis was the first indicator of AIDS in about 39% of the cases. About 80% of these patients were not being treated with highly active antiretroviral therapy (HAART) at the moment of histoplasmosis diagnosis, and about 42% of these patients died (Brilhante et al., 2012). Besides acting as a structural barrier, several research groups have demonstrated the importance of epithelial cells in modulating the immune system in various body tissues. In the lungs, for example, type II pneumocytes are among the cells that form the alveolar epithelium, and they are involved not only in surfactant production and repair of alveoli after a lung injury, but also in the immune response against particles and inhaled microorganisms (Mason, 2006). To participate in the hosts innate immunity, airway epithelial cells produce a wide range of inflammatory mediators, such as growth factors, cytokines, and chemokines, that promote recruitment and activation of immune cells to the sites of infection (Suzuki et al., 2008; Proud and Leigh, 2011). Recently, our group has demonstrated that the human fungal pathogen induces interleukin (IL)-6 and IL-8 secretion by the human lung epithelial cell line A549. This cytokine secretion was dependent on activation of some host cell signaling kinases, such as ERK 1/2 (extracellular signal-regulated kinase 1/2), p38 MAPK (p38 mitogen-activated protein kinase) and PKC (protein kinase C ; Maza et al., 2012; Alcantara et al., 2015). Later, we demonstrated that integrins are one type of receptor involved in the secretion of IL-6 and IL-8 (Barros et al., 2016). Papain Inhibitor In addition, promoted an increase of integrin expression in these epithelial cells, and clustering of 3 and 5 integrins into host membrane rafts was also observed in the presence of this fungus (Barros et al., 2016). Integrins are heterodimeric transmembrane glycoproteins consisting of and subunits. In mammals, 18 and 8 integrin subunits non-covalently dimerize to form 24 different receptors. Integrins, a major class of receptors involved in cell adhesion to other cells or to extracellular matrix, are able to bind to a wide variety of ligands, including.