Abstract
BackgroundDendritic cells (DCs) can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood.FindingsTo analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p < 0.05) up regulation following infection with M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS) from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation.ConclusionThese data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro.
Highlights
Dendritic cells (DCs) can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell
These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro
Flow Cytometric Analysis of Surface Markers All groups of DC (Immature DC alone, Immature DC infected with H37Rv M. tuberculosis strain, and stimulated with 1 μg/ml LPS for 48 hours) surface marker expression was assessed by flow cytometry (FACScan, BD) using direct double immunofluorescence labelling technique (CD40 FITC/CD80 PE, HLA DR FITC/CD54 PE, CD83 FITC/CD86 PE)
Summary
Dendritic cells (DCs) can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. Whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood. Mycobacterium tuberculosis is one of the most ubiquitous and extraordinarily effective human pathogens, with one-third of the global population being infected. DCs comprise a family of antigen presenting cells that act like ‘conductors’ of the immune response in their capacity to orchestrate signals derived from the different parts of the immune system [2]. At the immature stages of development, DCs resident in peripheral tissues are specialized in antigen capture, acting as sentinel cells (high intracellular MHC II, endocytosis, phagocytosis, high CCR1, CCR5, and CCR6; low CCR7 and low CD40, CD54, CD80, CD83, CD86 and CD58)
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