Obesity impairs resistance to Leishmania major infection in C57BL/6 mice.

Abstract

An association between increased susceptibility to infectious diseases and obesity has been described as a result of impaired immunity in obese individuals. It is not clear whether a similar linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity in the immune response to cutaneous L. major infection, we studied the ability of C57BL/6 mice submitted to a high fat and sugar diet to control leishmaniasis. Mice with diet-induced obesity presented thicker lesions with higher parasite burden and more inflammatory infiltrate in the infected ear when infected with L. major. We observe no difference in IFN-{gamma} or IL-4 production by draining lymph node cells between control and obese mice, but obese mice presented higher production of IgG1 and IL-17. A higher percentage of in vitro-infected peritoneal macrophages was found when these cells were obtained from obese mice when compared to lean mice. In vitro stimulation of macrophages with IL-17 decreased the capacity of cells from control mice to kill the parasite. Moreover, macrophages from obese mice presented higher arginase activity. Together our results indicate that diet-induced obesity impairs resistance to L. major in C57BL/6 mice without affecting the development of Th1 response.\n\nAuthor SummaryThe obesity is a public health problem and it is reaching extraordinary numbers in the world and others diseases are being involved and aggravated as consequence of obesity. What we know is that some diseases are more severe in obese people than in normal people. We did not know how obesity changes the profile of immune response to infectious agents, leading to the more severe diseases. That s why we decided to investigate how obese mice lead with Leishmania major infection. Leishmaniasis is a protozoa parasite infection considered a neglected disease. To try our hypothesis we gave a hipercaloric diet to induce obesity in C57BL/6 mice. After that, we injected L. major in the mice ear and followed the lesion for 8 weeks. We observed a ticker lesion and the cells from draining lymph node from obese mice produced more IL-17 than cells from normal mice. We also infected in vitro, macrophages from obese mice and stimulated the cells with IL-17, and we observed that the macrophages from obese mice are more infected by the L. major and it is worst in the presence of IL-17. Our results suggest that diet induced obesity decrease the resistance to infection.