Impact of opportunistic Mycobacterium tuberculosis infection on the phenotype of peripheral blood T cells of AIDS patients.

While the detrimental consequences of opportunistic tuberculosis (TB) in the course and outcome of HIV-1 infection are well studied, little information about the impact of the mycobacterial infection on the phenotype of T lymphocytes is available. In this study we analyzed by cytofluorimetry the peripheral blood T cell phenotype of 13 patients with AIDS, 23 HIV-1 negative patients with active pulmonary TB, nine HIV-1/Mycobacterium tuberculosis coinfected individuals, and 21 age- and sex-matched healthy controls. CD4+ T cells were equally depleted in AIDS and coinfection (P<0.001). The findings suggest a rescuing effect of the added mycobacterial infection. CD3 T cell loss was not observed in coinfection, whereas it was severe in AIDS (P<0.001). Similar (albeit less striking) effects were observed with other markers (CD45RA, CD45RO, and CD27) that were diminished in CD4+ T cells of AIDS patients. Apparent detrimental effects of the added mycobacterial infection were the increased expression of the proapoptotic molecule CD95 on CD4+ T cells, and decreased expression of the major costimulatory molecule CD28 on CD8+ T cells. In this work we show that M. tuberculosis infection modifies the T cell phenotype of the HIV-1 infected individual.

The 19-kDa antigen of Mycobacterium tuberculosis is a major adhesin that binds the mannose receptor of THP-1 monocytic cells and promotes phagocytosis of mycobacteria.

Identification of mycobacterial adhesins is needed to understand better the pathogenesis of tuberculosis and to develop new strategies to fight this infection. In this work, THP-1 monocytic cells were incubated with Mycobacterium tuberculosis culture filtrate proteins labelled with biotin and a dominant 19-kDa adhesin was found. This adhesin was characterized as the glycosylated and acylated 19-kDa antigen (Rv 3763). These findings were confirmed in assays with culture filtrate proteins and cell-wall fractions from a recombinant Mycobacterium smegmatis strain that overexpresses the 19-kDa antigen. Further, fluorescent microspheres coated with recombinant culture filtrate proteins adhere to cells in higher numbers than microspheres coated with native M. smegmatis proteins. The binding of the 19-kDa antigen to cells was inhibited with mannose receptor competitor sugars, Ca(2+) chelators and with a monoclonal antibody to the human mannose receptor. Phagocytosis assays showed high-level binding of bacilli to THP-1 cells that was inhibited with alpha-methyl-mannoside, mannan, EDTA and mAbs to the mannose receptor and to the 19-kDa M. tuberculosis antigen. Immunoprecipitation, cell-surface ELISA and immunostaining confirmed the expression of the mannose receptor by THP-1 cells. In conclusion, here we show that the macrophage mannose receptor, considered a pathogen pattern recognition receptor, may interact with mannose residues of mycobacterial glycoproteins that could promote the phagocytosis of mycobacteria.