RESPIRATORY BURST IN DENDRITIC CELLS AND ITS IMPACT IN THE ADAPTATIVE RESPONSE IN TUBERCULOSIS

ROMERO M; CORREA FEO L; BASILE J; LOPEZ B; RITACCO V; ALEMÁN M

Buzios

Congreso; XXXIX BRAZILIAN CONGRESS OF IMMUNOLOGY; 2014

Sociedad brasilera de Inmunología

Introduction: Tuberculosis (TB) remains the single largest infectious disease and a major global health problem caused by inhalation of aerosols containing the bacilli. Ten million new TB cases and 2 million deaths are estimated to occur each year, more than any time in history. Dendritic cells (DCs) are professional antigen-presenting cells that exhibit the ability to activate naive lymphocytes and may be differentiated from CD14+ monocytes in vitro. Infection of DCs with Mtb induces increased expression of costimulatory and maturation markers as well as numerous cytokines. On the other hand, TLR2 stimulation enhances the production of reactive oxygen species (ROS) that is accompanied by sustained phosphorylation of p38 mitogen-activated protein kinase (MAPK) which is in accordance with the fact that oxidative stress induces DCs maturation. In the present study, we characterize the DC responses induced by their interaction with Mtb reference strain H37Rv and two MDR clinical isolates, M and Ra, representative of widespread Mtb families in South America, i.e. Haarlem and Latin-American Mediterranean (LAM), being strain M able to generate further drug resistance and to disseminate aggressively. Methods: ROS production was evaluated by oxidation of 123Dihydrorhodamine (DHR), molecule expression by cytometry, and cytokine production by ELISA. Lymphocyte proliferation was determined by Mixed Leukocyte Reaction with allogeneic lymphocytes or by recall assay employing cells from PPD+ subjects and measured by [methyl-3H]thymidine] incorporation. Results: Mtb H37Rv induced the expression of CD83, CD86, HLA-DR, IL-12 and IFN (p