Obesity impairs resistance toLeishmania majorinfection in C57BL/6 mice

Abstract

23An association between increased susceptibility to infectious diseases and obesity has been 24 described as a result of impaired immunity in obese individuals. It is not clear whether a similar 25 linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity 26 in the immune response to cutaneous L. major infection, we studied the ability of C57BL/6 mice 27 submitted to a high fat and sugar diet to control leishmaniasis. Mice with diet-induced obesity 28 presented thicker lesions with higher parasite burden and more inflammatory infiltrate in the 29 infected ear when infected with L. major. We observe no difference in IFN-γ or IL-4 production 30 by draining lymph node cells between control and obese mice, but obese mice presented 31 higher production of IgG1 and IL-17. A higher percentage of in vitro-infected peritoneal 32 macrophages was found when these cells were obtained from obese mice when compared to 33 lean mice. In vitro stimulation of macrophages with IL-17 decreased the capacity of cells from 34 control mice to kill the parasite. Moreover, macrophages from obese mice presented higher 35 arginase activity. Together our results indicate that diet-induced obesity impairs resistance to L. 36 major in C57BL/6 mice without affecting the development of Th1 response. 37 38 39 4 40 Author Summary 41The obesity is a public health problem and it is reaching extraordinary numbers in the world 42 and others diseases are being involved and aggravated as consequence of obesity. What we 43 know is that some diseases are more severe in obese people than in normal people. We did not 44 know how obesity changes the profile of immune response to infectious agents, leading to the 45 more severe diseases. That`s why we decided to investigate how obese mice lead with 46 Leishmania major infection. Leishmaniasis is a protozoa parasite infection considered a 47 neglected disease. To try our hypothesis we gave a hipercaloric diet to induce obesity in 48 C57BL/6 mice. After that, we injected L. major in the mice ear and followed the lesion for 8 49 weeks. We observed a ticker lesion and the cells from draining lymph node from obese mice 50 produced more IL-17 than cells from normal mice. We also infected in vitro, macrophages from 51 obese mice and stimulated the cells with IL-17, and we observed that the macrophages from 52 obese mice are more infected by the L. major and it is worst in the presence of IL-17. Our 53 results suggest that diet induced obesity decrease the resistance to infection. 54 55 157 20 °C. 158 159 Histology

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