Regulation of Toll-Like Receptor 2 Expression by Macrophages FollowingMycobacterium aviumInfection

Abstract

Recent studies have implicated Toll-like receptors (TLR), especially TLR2 and TLR4, as sentinel receptors that signal the interaction of macrophages with bacterial pathogens via a NF-κB-mediated pathway. The regulation of TLR gene expression, however, has not been intensively studied. Here, we report that TLR2 mRNA was induced following infection of murine macrophages with Mycobacterium avium. The changes in TLR2 mRNA correlated with an increase in TLR2 surface expression. Infection with M. avium resulted in a concomitant decrease in TLR4 mRNA. The effect of M. avium infection on TLR2 mRNA appeared to be mediated, in part, by TLR2 because the induction of the mRNA was partially blocked by preincubation of the macrophages with an anti-human TLR2 Ab. In contrast, the effect of LPS stimulation was mediated via TLR4 because infection of macrophages from LPSd mice, which do not express active TLR4, resulted in an increase in TLR2 mRNA, while treatment of macrophages from these mice with LPS failed to induce TLR2 mRNA. Several cytokines, including TNF-α, IL-1α, and GM-CSF, but not IFN-γ, induced TLR2 mRNA. M. avium infection resulted in the induction of TLR2 mRNA by macrophages from both TNFRI knockout and NF-κB p50 knockout mice.

Innate Immune Recognition of Invasive Bacteria Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice

“…46,47 However, the importance of the TLR-mediated response during P gingivalismediated periodontal disease is unknown. Studies using Mycobacterium avium and Haemophilus influenzae support the proposition that bacterial infection leads to increased expression of TLRs 12,13 and that these TLRs play a role in further innate immune sensing during Crohn's disease and tuberculosis. 48,49 Our studies demonstrate that during P gingivalis-accelerated atherosclerosis, the host modulates the expression of TLRs, but only to invasive organisms.…”

“…10 TLRs are an emerging group of pattern recognition molecules that mediate the innate host response to microbes 11 and are selectively upregulated after infection. 12,13 Chronic infectious diseases, including periodontal disease, are associated with increased risk for CVD. 14 -18 However, this connection remains speculative because of conflicting reports.…”

Transcriptional expression levels of chicken collectins are affected by avian influenza A virus inoculation

“…In mammals, an up regulation of collectins has frequently been observed in both bacterial and viral infections (Murray et al, 2002;Grubor et al, 2004), which is usually interpreted as a direct response of the host to increase its defense against the incoming pathogens. A down regulation of collectins upon infection is less frequently reported, but could reflect a survival strategy of the pathogen to overcome the host's hostile environment, as has been described for other innate immune proteins such as Tolllike receptors and defensins (Wang et al, 2000;Shin et al, 2007). However, whether this applies to AIV in the chicken lung and why the altered expression of chicken (col)lectins is tissue specific is not clear at this moment and requires further investigation.…”

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

“…These have been shown to induce TLR2 specific responses measured as NFjB activation in macrophages and endothelial cells (Faure et al, 2001;Wang et al, 2000). We tested the ability of these cytokines to induce TLR2 expression by GCV-purified astrocytes.…”