How can tuberculosis bacteria interfere with immune cells' ability to reveal their presence?

Details

Mycobacterium tuberculosis survives inside macrophages despite acquired CD4-positive T-cell immunity, which controls the organism but does not eliminate it. Interferon-gamma (IFN-gamma) plays a central role in defenses against M. tuberculosis by activating macrophages and regulating antigen processing through major histocompatibility complex class II (MHC-II). M. tuberculosis interferes with IFN-gamma receptor signaling in macrophages, but the molecules responsible for this inhibition have been poorly defined.

In a laboratory study of human macrophages, researchers examined the effects of exposure to the 19-kDa lipoprotein from M. tuberculosis and used a monoclonal antibody specific for Toll-like receptor 2 (TLR-2) to test its involvement. The lipoprotein inhibited IFN-gamma-regulated expression of both HLA-DR protein and HLA-DR mRNA. This inhibition was associated with decreased processing and presentation of soluble protein antigens and M. tuberculosis bacilli to MHC-II-restricted T cells.

Inhibition of HLA-DR required prolonged exposure to the 19-kDa lipoprotein and was blocked by the TLR-2-specific monoclonal antibody. The lipoprotein also inhibited IFN-gamma-induced expression of Fc gamma RI.

The study concludes that the 19-kDa lipoprotein activates TLR-2, allowing M. tuberculosis to inhibit IFN-gamma receptor signaling in human macrophages. This results in decreased MHC-II antigen processing and recognition by MHC-II-restricted CD4 T cells. These findings provide a mechanism for M. tuberculosis persistence in macrophages.