Abstract
Introduction: Though PE and PPE families have been thought to play important roles in mycobacterial pathogenesis from an antigenic as well as immunological view point, there has not been much information available regarding their physiological relevance, more so in the light of the fact that mycobacteria have been highly successful in devising strategies of immune evasion. One of the PPE proteins, Rv1196 (PPE18 or mtb39a) was found to be expressed during infection and present exclusively in M. tuberculosis and M. bovis BCG but not in other mycobacterial species. Further, the microarray studies indicate that Rv1196 is one of the proteins involved in maintaining long term survival of M. tuberculosis within the host. Since Th2 plays an important role in activating M. tuberculosis pathogenesis, we have evaluated the role of Rv1196 protein to interact with macrophage and affect the Th2 balance. Method: Cytokine induction was measured by enzyme immunoassay (EIA). Interacting receptor on macrophages were identified by flow cytometry and coimmunoprecipitation assay using specific antibody. The p38 MAPK and ERK 1/2 and JNK signaling was examined by Western blotting and flow cytometry Results: We demonstrate that the PPE protein, Rv1196 stimulates macrophages to secrete interleukin (IL)-10 cytokine, which favors a Th2 T-cell response congenial for mycobacterial survival. However, it does not significantly affect the production of inflammatory cytokines like IL-12, TNFas well as nitric oxide production. IL-10 induction was found to be dependent on specific interaction of Rv1196 protein to the toll-like receptor (TLR) 2 on membrane. We found that an early and sustained activation of p38 MAPK (but not ERK 1/2 and JNK) downstream of TLR2 was critical for triggering of IL-10 by Rv1196. Conclusion: Our data suggest a unique role of the M. tuberculosis PPE protein in eliciting an anti-Th1 response critical for survival of the bacteria.
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