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Morphological and functional characterization of immature myeloid cells in severe tuberculosis

Grant number: 17/09110-4
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): November 01, 2017
Effective date (End): October 31, 2018
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Caio César Barbosa Bomfim
Supervisor abroad: Alan Sher
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : National Institutes of Health, Bethesda (NIH), United States  
Associated to the scholarship:14/22986-8 - Role of myeloid derived suppressor cells and its purinergic regulation in severe tuberculosis, BP.DR

Abstract

Tuberculosis, a disease caused by acid-fast bacilli, has a high prevalence worldwide. It is estimated that Mycobacterium tuberculosis bacillus infects a quarter of the world's population, and about 10% of these individuals are expected to develop the disease in the course of their lives. Recently, we observed that C57BL/6 mice infected with the clinical MP287/03 isolate of Mycobacterium bovis (Mbv), which induces a very aggressive form of the disease, presented a huge lung infiltration of cells with characteristics similar to those of myeloid derived suppressor cells (MDSCs). MDSCs are immature myeloid cells that have immunosuppressive activity. However, little is known about the role of immature myeloid cells in TB development. Moreover, one of the main difficulties to understand the pathogenesis of severe TB is the fact that necrotic granulomas are unusual in most murine models of TB. Thus, the aim of this study is to compare, phenotypically and functionally, the immature myeloid cell population in heavily infected C57BL/6 mice with that in kramnik mice and marmoset primates, which develop diseases that better recapitulate the human TB. These animals will be analyzed according to TB progression and the presence of MDSC-like cells in the lungs, which will be characterized functionally. This is relevant issue because the understanding of the mechanisms involved in the pathogenesis of severe TB opens the perspectives for the development of new therapeutic approaches aiming to attenuate the disease progression. These analyses require manipulation of mycobacteria and infected samples in biosafety level 3 (BSL-3) laboratory equipped with confocal microscopy, cell sorter device and image streaming that are not available in Brazil. This opportunity will give us the necessary knowledge to determine the role of MDSCs in severe TB, which is the goal of my PhD project in Brazil.