Efeitos da testosterona na função efetora de macrófagos humanos no modelo de infecção in vitro por Leishmania amazonensis

Abstract

Several studies describe sex differences in the prevalence of infectious diseases, mainly by intracellular pathogens, with a higher frequency in males. This difference is frequently interpreted as a result of an epidemiological factors, like a higher exposure to men to the pathogens. However, in view of the demonstration of the hormones influence and their cellular receptors on the innate and adaptive immune response, the interest in studies to evaluate host interaction with pathogens and the hormonal interference in immune response is relevant, as it would explain the sexual variation of response to pathogens in a biological context . Thus, in order, the goal of this study was evaluating the influence of testosterone on human macrophage effector function using as a model in vitro infection for Leishmania amazonensis. Blood samples were collected from healthy individuals (n= 11) with mean age about 29,7 ± 7,21. Mononuclear cells from these individuals were fractionated and cultured with increasing doses of testosterone (0 to 160 nM) until macrophage differentiation. Subsequently, in vitro infection with a fluorescent Leishmania amazonensis strain (GFP) was performed and then samples analysis by flow cytometry to detect the frequency of infected macrophages and parasite load (for median of fluorescence intensity-MFI). In addition, the phenotype profile of this cells were performed after stimulus of testosterone using surface molecules (CD40 and CD163) and intracellular (IL4, IL10, IL12 and TNFα) antibody staining, as well as gene expression (mRNA) analysis by RT-PCR for transcription factors, cytokines and cell signaling proteins (TREM-1, AIF-1, TLR4, IL10, STAT6, SOCS1, SOCS3, IFR4 e IRF5). Testosterone treatment (doses above 80 nM) promotes a significant increase in the percentage of infected cells. Moreover, we observed a decrease on CD40 surface marker and higher expression of mRNA of SOCS1 transcription factor as a decrease in IFR5 mRNA expression, suggesting that testosterone have an effect on Leishmania infection, by inducing a suppression of macrophage microbicidal function. Therefore, this data suggests a role of immunoendocrine axis, in particular testosterone, as a potential facilitator of infection in the interaction between the Leishmania and macrophages.