Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis

Mycobacterium tuberculosis (MTB) induces vigorous immune responses, yet per sists inside macrophages, evading host immunity. MTB bacilli or lysate was found to inhibit macrophage expression of class II MHC (NMC-H) molecules an d MHC-II Ag processing. This report characterizes and identifies a specific component of MTB that mediates these inhibitory effects. The inhibitor was extracted from MTB lysate with Triton X-114, isolated by gel electroelutio n, and identified with Abs to be MTB 19-kDa lipoprotein. Electroelution- or immunoaffinity-purified MTB 19-kDa lipoprotein inhibited MHC-II expression and processing of both soluble Ags and Ag 85B from intact MTB bacilli. Inh ibition of MHC-II Ag processing by either MTB bacilli or purified MTB 19-kD a lipoprotein was dependent on Toll-like receptor (TLR) 2 and independent o f TLR 4. Synthetic analogs of lipopeptides from Treponema pallidum also inh ibited Ag processing. Despite the ability of MTB 19-kDa lipoprotein to acti vate microbicidal and innate immune functions early in infection, TLR 2-dep eadent inhibition of MHC-II expression and Ag processing by MTB 19-kDa lipo protein during later phases of macrophage infection may prevent presentatio n of MTB Ags and decrease recognition by T cells. This mechanism may allow intracellular MTB to evade immune surveillance and maintain chronic infecti on.