02 July 2009
HIV may directly impair the body’s response to Mycobacterium tuberculosis through two innate immune factors, interleukin 10 (IL-10) and BCL-3, according to results of lab studies by Harvard researchers. They proposed that BCL-3 may be a target for agents aimed at preventing or treating TB.
M tuberculosis-triggered apoptosis (cell death) of macrophages is a critical defense response against TB. An impaired macrophage response could make people more vulnerable to M tuberculosis.
To see whether this mechanism plays a role in making people with HIV vulnerable to TB, the Harvard team collected alveolar macrophages from the lungs of people with asymptomatic HIV infection and from healthy people without HIV. Apoptosis of the macrophages was significantly decreased in HIV-infected people.
To find out why, the researchers analyzed lung specimens and found significantly higher levels of IL-10 in people with HIV. High IL-10 levels reduced release of another immune regulator, tumor necrosis factor (TNF), in healthy alveolar macrophages. Adding TNF to the cells partially reversed the impact of IL-10 on macrophage apoptosis.
IL-10 also increased levels of BCL-3 in macrophages, and lower BCL-3 increased M tuberculosis-mediated release of TNF. BCL-3 levels in macrophages of HIV-infected people were higher than in macrophages of healthy people without HIV.
“Taken together,” the researchers propose, “these data suggest that elevated lung levels of IL-10 may impair M tuberculosis-mediated alveolar macrophage apoptosis in HIV through a BCL-3-dependent mechanism. BCL-3 may represent a potential therapeutic target to treat or prevent M tuberculosis disease in HIV+ persons.”
Source: Naimish R. Patel, Katharine Swan, Xin Li, Souvenir D. Tachado, Henry Koziel. Impaired M. tuberculosis-mediated apoptosis in alveolar macrophages from HIV+ persons: potential role of IL-10 and BCL-3. Journal of Leukocyte Biology. 2009;86:53-60.
For the study abstract
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