Mycobacterium tuberculosis heat shock protein 60 modulates immune response to PPD by manipulating the surface expression of TLR2 on macrophages

Abstract

The T-helper (Th) 1 T-cell response to purified protein derivative (PPD) is known to be suppressed in tuberculosis patients which favours intracellular survival of the bacilli. We demonstrate that the Mycobacterium tuberculosis heat shock protein 60 (Mtbhsp60) plays an important role to skew the anti-PPD T-cell response towards the Th2 type when macrophages were used as antigen presenting cells. We found that the PPD-induced IL-12 p40 was downregulated in macrophages by Mtbhsp60. The Mtbhsp60 preferentially induced Toll-like receptor (TLR) 2 without affecting TLR4 expression on macrophages. Interaction of Mtbhsp60 with TLR2 resulted in significant suppression of nuclear c-rel and consequently IL-12 p40 levels in PPD-activated macrophages. Our findings reveal a unique role of the Mtbhsp60 favouring development of Th2 type response by upregulating surface expression of TLR2 on macrophages which could be a survival strategy adopted by the bacilli.