
-   Activation of Toll-like receptor 2/1 (TLR2/1) on monocytes induces a vitamin D dependent antimicrobial activity against intracellular mycobacteria. TLR activation of monocytes triggers induction of the defensin beta 4 gene (DEFB4), requiring convergence of the IL-1beta and vitamin D receptor (VDR) pathways. TLR2/1 activation triggered IL-1beta activity, involving the upregulation of both IL-1beta and IL-1 receptor, and downregulation of the IL-1 receptor antagonist [PMID: 19503839].
-   Toll-like receptors (TLRs) on intestinal dendritic, mononuclear, and epithelial cells recognize bacterial ligands and damaged tissues, thus activating the inflammatory response. Signal transduction via molecules of the Toll-like receptor (TLR)/interleukin 1 receptor (IL-1R) pathway is critical for activation of APCs, which is essential for initiation of cell-mediated immune responses to pathogens. The bacterial CpG-DNA activates the TLR/IL-1R signaling pathway via the molecules myeloid differentiation marker 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6), leading to activation of kinases of the IkappaB kinase complex and the c-jun NH(2)-terminal kinases [PMID: 10952730].

## Summary

TLR1, a Toll-like receptor, functions in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) such as diacylated and triacylated lipopeptides, often present in bacterial infections. In the colon, where exposure to a variety of microbes is common, TLR1 works in tandem with TLR2 to detect these PAMPs, activating the immune response. This response includes the production of cytokines and the initiation of signaling pathways that lead to inflammation, necessary for combating pathogens. For example, in ulcerative colitis, a variant of TLR1 (R80T) is associated with pancolitis, a condition of widespread inflammation in the colon.

In cases of toxic events or disease in the colon, such as necrotizing enterocolitis (NEC) in neonates, an upregulation of TLR1 mRNA is observed. This upregulation likely serves as a response mechanism to increased bacterial presence or microbial activity in the gut, triggering an immune response to protect the host. The induced TLR1 expression enhances the detection of bacterial lipopeptides, thereby activating the immune system to address the infection or inflammation. However, this can also lead to excessive inflammation, exacerbating conditions like NEC or inflammatory bowel diseases.
