Ethanol modulates the effector functions of human monocyte-derived macrophages in response to Paracoccidioides brasiliensis yeast cells

Author(s)

de Castro, Livia Furquim ^[1] ; Mathias, Kamila de Araujo ^[2] ; Nunes, Julia Vieira ^[2] ; Bergamasco Galastri, Ana Lucia ^[2] ; Leandro da Silva, Dennis Henrique ^[1] ; Alegrini Longhi, Larissa Nara ^[1] ; de Souza Lima Blotta, Maria Heloisa ^[1] ; Mamoni, Ronei Luciano ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, Fac Med Sci, Dept Clin Pathol, UNICAMP, BR-13083970 Campinas, SP - Brazil

^[2] Fac Med Jundiai FMJ, Dept Morphol & Basic Pathol, BR-13202550 Jundiai, SP - Brazil

• Document type: Journal article
• Source: Medical Mycology; v. 59, n. 8, p. 773-783, AUG 2021.
• Web of Science Citations: 2

Abstract

We aimed to investigate the effects of ethanol and its metabolites (beta-hydroxybutyrate and sodium acetate) in the effector functions of macrophages in response to Paracoccidioides brasiliensis yeast cells and to determine their influence in the development of the adaptive response. Purified peripheral blood monocytes were differentiated into macrophages and were treated with ethanol, beta-hydroxybutyrate, and sodium acetate, and stimulated with P brasiliensis yeast cells and evaluated for their phenotypic characteristics, functional activity, and capability to induce T cells activation/differentiation. We found that the ethanol treatment diminished the expression of HLA-AB, HLA-DR, CD80, and CD86, modulating the expression of dectin-1, as well as Syk phosphorylation. The ethanol treatment increased the phagocytic activity, expression of CD206, and IL-10 production; however, reduced ROS production, fungicidal activity, caspase-1 cleavage, and iL1 beta and IL-6 production. Our data also showed that the presence of ethanol reduced the differentiation of Th1 and Th17 cells and increased the frequency of Th2 cells. Our results indicated that ethanol exposure could suppress effector function of macrophages, possibly leading to the polarization of M2 macrophages. The ethanol modulates the expression of costimulatory and antigen-presentation molecules and interferes with the NLRP3 inflammasome. Altogether, these alterations affect the development of the adaptive response, decreasing the frequency of IL-17, IL-22, and IFN-gamma producing cells, and increasing the frequency of IL-4 producing cells. Therefore, exposure to ethanol can impair the capability of macrophages to exert their effector functions and activate the acquired response related to resistance to P brasiliensis infection. (AU)

• FAPESP's process: 15/18788-9 - Evaluation of ethanol effects on the effector response of macrophages to the dimorphic fungus P. brasiliensis .
• Grantee: Lívia Furquim de Castro
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/24286-0 - Participation of the inflammasome NLRP3 and cytokines from the IL-1 family in the infammatory response induced by the pathogenic fungi Paracoccidioides brasiliensis and Candida albicans
• Grantee: Ronei Luciano Mamoni
• Support Opportunities: Regular Research Grants