Regulation of toll-like receptor 2 expression by macrophages following Mycobacterium avium infection

Recent studies have implicated Toll-like receptors (TLR), especially TLR2 a nd TLR4, as sentinel receptors that signal-the interaction of macrophages w ith bacterial pathogens via a NF-kappaB-mediated pathway. The regulation of TLR gene expression, however, has not been intensively studied. Here, we r eport that TLR2 mRNA was induced following infection of murine macrophages with Mycobacterium avium, The changes in TLR2 mRNA correlated with an incre ase in TLR2 surface expression. Infection with M. avium resulted in, a conc omitant decrease in TLR4 mRNA, The effect of M, avium infection on TLR2 mRN A appeared to be mediated, in part, by TLR2 because the induction of the mR NA was partially blocked by preincubation of the macrophages with an anti-h uman TLR2 Ab, In contrast, the effect of LPS stimulation was mediated via T LR4 because infection of macrophages from LPSd mice, which do not express a ctive TLR4, resulted in an increase in TLR2 mRNA, while treatment of macrop hages from these mice with LPS failed to induce TLR2 mRNA, Several cytokine s, including TNF-alpha, IL-1 alpha, and GM-CSF, but not IFN-gamma, induced TLR2 mRNA, M, avium infection resulted in the induction of TLR2 mRNA by mac rophages from both TNFRI knockout and NF-kappaB p50 knockout mice.