Papel de fatores solúveis associados à obesidade na ativação macrofágica durante infecção por Trypanosoma cruzi

Abstract

Obesity represents a worrying picture in the world public health with increasing numbers in various sectors of society. In Brazil the numbers are worrying, in 2014 the rates of overweight and obesity were at 52% and 17%, respectively. Obesity is characterized as metabolic syndrome and a low-grade inflammatory process known as meta-inflammation. Macrophage activation by adipocyte-secreted soluble factors (FSA) is important in the differentiation of monocytes into characteristic adipose tissue macrophages. Moreover, a change in polarization of macrophages from M2 profile to M1 profile is observable characteristics during obesity. Metabolic dysfunctions are directly related to pro-inflammatory cytokine production and although the impact of obesity on metabolic and cardiovascular diseases is well known, its role in immune system activation during the course of infectious diseases is poorly understood. Several diseases may be compromised by the modulation of factors associated with obesity, including Chagas disease. This disease is a neglected zoonosis for reaching low-class sectors of little public interest. It is an endemic disease in Latin America, but it is present in northern hemispheric countries due to factors such as the migratory process, transfusions, among others. Thus, this paper aims to draw a correlation between FSA and macrophage activation during Trypanosoma cruzi infection. Also, understand how FSAs may or may not contribute to the progression of Chagas disease. Focusing on lipid metabolism modulation, cytokine production and expression of M1 and M2. macrophage profile markers In this study we differentiated NIH3T3-L1 cells into adipocytes and used the supernatant obtained from them to stimulate peritoneal macrophages infected or not with Trypanosoma cruzi. The results showed that Trypanosoma cruzi infection induces higher biogenesis of lipid body at 24, 48 and 72 hours and was potentiated in the presence of FSA. Infection induced increase in IL-10 cytokine production at 24, 48 and 72 hours only in the presence of FSA. For TNFα cytokine, there was an increase in infected groups, an effect that was not modulated by the presence of FSA, whereas cytokine KC increased in infected groups and was modulated by FSA only within 24h. In addition, we found that the infection-induced an increase in nitric oxide (NO) production observed by the increase of nitrite production by activated macrophages and that this increase was modulated by FSA only within 24 hours. Infection also induced PPARγ expression at 24, 48 and 72 hours and was modulated by FSA at 72h. Thus our results suggest a modulating role of adipocyte-secreted factors in macrophage activation, attributed to increased lipid body biogenesis, PPARγ expression, cytokine syntheses such as TNF-α and KC and negative modulation of IL-10 production during Trypanosoma cruzi infection in vitro.