Mycobacterium tuberculosis 19-kDa lipoprotein induces Toll-like receptor 2-dependent peroxisome proliferator-activated receptor gamma expression and promotes inflammatory responses in human macrophages

摘要

Mycobacterium tuberculosis (M.tb) enhances its survival in macrophages by suppressing immune responses, in part through its complex cell wall structures. M.tb 19-kDa lipoprotein (P19), a component of the complex cell wall structures of M.tb, is a Toll-like receptor (TLR) agonist, and may induce immune responses through TLR2. Furthermore, the activation of peroxisome proliferator-activated receptor (PPAR) is also involved in M.tb-induced immune responses in macrophages. In the present study, specific agonists/antagonists and siRNA were used to investigate the role of PPAR in P19-induced immune responses in human macrophages, including TLR2 activation, p38 phosphorylation and cytokine production. In the present study, PPAR expression, p38 phosphorylation and cytokine production were upregulated following M.tb H37Rv infection or P19 treatment. By pretreating macrophages with a specific PPAR agonist or antagonist, it was demonstrated that phosphorylation and IL-6 production are modulated in macrophages by PPAR activity. Following TLR2 knockdown in macrophages, the expression of PPAR was significantly decreased in the presence or absence of P19 treatment. Furthermore, p38 phosphorylation and cytokine production were significantly reduced in TLR2 knockdown macrophages following P19 treatment. It was demonstrated in the current study that PPAR was induced and activated by M.tb infection and that P19-induced PPAR expression, p38 phosphorylation and cytokine production in macrophages are dependent on TLR2. These findings suggest a role for PPAR and TLR2 in P19-induced p38 phosphorylation and cytokine production, thereby potentially influencing M.tb pathogenesis.