Networked T cell death following macrophage infection by Mycobacterium tuberculosis

The loss of T cells following infection by Mycobacterium tuberculosis (Mtb) impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity

The loss of T cells following infection by Mycobacterium tuberculosis (Mtb) impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. There are a known number of mechanisms that contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs, however the extent to which Mtb infection of human macrophages affects T cell viability is not well characterised. These researchers from Trinity Institute of Molecular Medicine in Dublin, Ireland had previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. Therefore in this study they went further and examined the influence of infected human alveolar macrophages on T cells. To do this they infected primary human alveolar macrophages or PMA-differentiated THP-1 cells with Mtb H37Ra, and then prepared cell-free supernatants. They found that the supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis which did not require input from TNF-? or Fas. The supernatant cytotoxic signals were also found to be heat-labile. Thus showing that Mtb-Infected macrophages may contribute to the immunosuppression seen in tuberculosis as well as interfere with microbial eradication in the granuloma.
 
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