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Interplay of the immune response in the obesity and tuberculosis

Grant number: 15/00774-1
Support type:Regular Research Grants
Duration: August 01, 2015 - July 31, 2017
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:João Santana da Silva
Grantee:João Santana da Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:Daniela Carlos Sartori ; Isis Do Carmo Kettelhut


Among bacterial infections, tuberculosis is the disease which causes the highest number of deaths. Even being extensively studied considering the relationship of the host with the pathogen Mycobacterium tuberculosis, etiologic agent of this disease, the factors that contribute for the development of active and progressive tuberculosis in immune competent individuals are complex and still unclear. Collected data obtained from experimental models show that M. tuberculosis infection generates cellular immune response, characterized, in general, by the presence of classically activated macrophages (M1) and IFN-gama-producing CD4+ T lymphocytes. This pattern of immune response is associated with protection of the host. However, cellular immune response induces also an intense inflammation in this chronic disease. Among the social and economic factors associated with the greater risk to develop or reactivate tuberculosis are malnutrition and alcoholism. A better understanding of the factors that affect the immune response during the infection is essential in attempt to search for new therapies for tuberculosis. In this scenario, there is a new field described as Immune metabolism. In the last 25 years, there was an increase in the incidence of obesity in the world. In obese individuals, the adipose tissue is constituted, beyond adipocytes, of leukocytes, such as macrophages and T cells. Metabolic dysfunctions in obese individuals are directly associated with increased levels of proinflammatory cytokines. The inflammation triggered by obesity is described as metainflammation, which is characterized by lower amplitude that those existent in immune-mediated diseases. The metainflammation is associated with the development of chronic diseases, infectious or not. However, the association between obesity and M. tuberculosis infection remains to be better defined. Our initial hypothesis is that the inflammation triggered by obesity could be deleterious and could induce tuberculosis progression, although an inverse association between weight and tuberculosis had been described in epidemiological studies. Moreover, the obesity may down modulate the role of T lymphocytes. Therefore, in attempt to understand better the role of inflammation in the tuberculosis, our aim is to study how the obesity affects the susceptibility or resistance and intrinsic mechanisms to M. tuberculosis infection. (AU)