Paracoccidioidomycosis (PCM) is a systemic inflammatory granulomatous disease caused by fungi from Paracoccidioides genus, it affects mainly immunocompetent individuals, being the major cause of systemic mycosis of Latin America, particularly in Brazil. PCM is characterized by several clinical manifestations, and can be classified in two main clinical forms: the chronic form (CF), more localized, and the acute form (AF), more severe and disseminated. These clinical manifestations present different immune responses. While AF is characterized by commitment of immune response, associated with a predominant Th2/Th9 response, with high production (in vitro) of cytokines that suppress the cellular immune response (IL-4, IL-5, IL-10 and TGF-²). The CF is characterized by the development of a heterogeneous immune response, with predominant participation of Th17/Th22 cells (producing IL-17 and IL-22), besides cytokines characteristics of Th1 response (IFN-³, TNF-± and IL-2) and variable amounts of IL-10 and IL-4. Although the different acquired immune responses associated with susceptibility and resistance to the infection are relatively well established, the mechanisms responsible for the induction of these responses remain unclear. The induction of the adaptive immune response depends on events that occur at the beginning of the infection, which are promoted by cells of the innate immune response. Among the cells that participate of these initial events in PCM (as well in others infections) macrophages present a preponderant role. Environmental factors could interfere in the effectors functions of these cells and, consequently, can influence the polarization of adaptive response. Studies have demonstrated that both acute and chronic exposure to ethanol (alcohol) is strongly associated with the suppression of the immune system. Ethanol consumption has been associated with susceptibility to lung infections caused by Pneumococcus, Klebsiella pneumoniae, Streptococcus pneumoniae, and Mycobacterium tuberculosis. In PCM, alcoholism is considered a risk factor for evolution of disease, mainly in the chronic form; however, there are not studies that have demonstrated the ethanol effects on immune response of human cells against the fungus P. brasiliensis. This study aim to investigate the effects of ethanol and compounds derivate from ethanol metabolism (acetaldehyde, sodium acetate, and ²-hydroxybutyrate) on effectors' functions of macrophages in response to the fungus P. brasiliensis, and determine their influence in the development of the adaptive immune response. Thus, this study can contribute to the understanding of mechanisms involved in the suppression of the immune response caused by alcohol (ethanol) consumption and its relationship with susceptibility to infection observed in patients with the CF of PCM.
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