Role of dendritic cells in the differentiation of CD4+ cell populations in mice with different ability to generate cellular immune response against Mycobacterium tuberculosis

Abstract

In our laboratory we have used animals which have different ability to generate Th1 immune responses and distinct ability to controlling Mycobacterium tuberculosis infection with the aim to characterize immunological factors and mechanisms involved in the regulation of immune response. Our results show that BALB/c mice, which do not control infection at the late phase (70 days), had down modulation in IFN-gamma production and in the expression of IFN-gamma receptor in lung, increase in IL-10 synthesis and in the expression of the receptor for this cytokine. Moreover, spleen regulatory T cells obtained from infected BALB/c mice were more suppressive, causing profound decrease in IFN-gamma production, than regulatory T cells obtained from infected C57BL/6 mice. On the contrary, C57BL/6 mice secreted more IFN-gamma and IL-17 and controlled the infection at the late phase. Therefore we addressed to the role of dendritic cells in the induction of adaptive immune response in these mouse strains. Beyond the first and the second signal, dendritic cells also provide a third signal, described by their ability to drive the differentiation of CD4+ T cell populations based on the cytokines secreted or soluble mediators found in the microenvironment. In this way, our hypothesis is to evaluate whether the number and functional capacity of dendritic cells are different in C57BL/6, BALB/c and DBA/J2 mice. Consequently, we will study if the number and the functional capacity of these cells would be associated with the different magnitude of Th1, regulatory T cells and Th17 cells, observed in infected mice (BALB/c and C57BL/6). Additionally, we will study if the retinoic acid could interfere in the different pattern of immune response among mouse strains studied.The comprehension of the mechanisms that contribute for progression or control of tuberculosis may incentive and promote the design of new strategies of prophylactic or therapeutic intervention for this disease. Moreover, we expect that the data generated with the development of this project can contribute for a better understanding of the pathology caused by M. tuberculosis and in the search for new immunological markers that may predict latent or active infection. (AU)