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Evaluation of ethanol effects on the effector response of macrophages to the dimorphic fungus P. brasiliensis .

Grant number: 15/18788-9
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2015
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Ronei Luciano Mamoni
Grantee:Lívia Furquim de Castro
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

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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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE CASTRO, LIVIA FURQUIM; MATHIAS, KAMILA DE ARAUJO; NUNES, JULIA VIEIRA; BERGAMASCO GALASTRI, ANA LUCIA; LEANDRO DA SILVA, DENNIS HENRIQUE; ALEGRINI LONGHI, LARISSA NARA; DE SOUZA LIMA BLOTTA, MARIA HELOISA; MAMONI, RONEI LUCIANO. Ethanol modulates the effector functions of human monocyte-derived macrophages in response to Paracoccidioides brasiliensis yeast cells. Medical Mycology, v. 59, n. 8, p. 773-783, . (15/18788-9, 13/24286-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CASTRO, Lívia Furquim de. Evaluation of the effects of ethanol and metabolites on the effector and modulating response of macrophages to the dimorphic fungus Paracoccidioides brasiliensis. 2019. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.

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