Tlr1-KO Mouse

Tlr1, Toll-like receptor 1, is a key component in the innate immune system. It often forms heterodimers with Tlr2, enabling the recognition of a variety of microbial ligands such as bacterial lipoproteins. This recognition activates signaling cascades, like the MAPK and NF-κB pathways, which are crucial for the activation of multiple inflammatory genes, playing an essential role in regulating both innate and adaptive immunity [2,3].

In ulcerative colitis (UC) studies, Lactobacillus johnsonii was found to alleviate colitis by activating CD206 + macrophages-IL-10 through the Tlr1/2-STAT3 pathway. Tlr1/2 was essential for the activation of STAT3 and recognition of L. johnsonii by macrophages. Clinically, there was a positive correlation between the abundance of L. johnsonii and the expression level of Tlr1/2 in UC tissues [1]. In locally advanced colorectal cancer, the TLR1-N248S polymorphism (rs4833095), causing loss-of-function in HMGB1-mediated TLR1-TLR2 signaling, influenced the therapeutic efficacy of adjuvant chemotherapy, with patients having a high risk of distant metastasis within 5 years. Defective Tlr1 on dendritic cells impaired their maturation ability and reduced the secretion of IFNγ from T cells to eradicate tumor cells [4].

In conclusion, Tlr1 is vital in the innate immune response through ligand recognition and activation of downstream signaling. Research using models, such as observing the effects of polymorphisms similar to loss-of-function scenarios, has revealed its significance in diseases like UC and locally advanced colorectal cancer, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Jia, Ding-Jia-Cheng, Wang, Qi-Wen, Hu, Ying-Ying, Chen, Shu-Jie, Wang, Liang-Jing. . Lactobacillus johnsonii alleviates colitis by TLR1/2-STAT3 mediated CD206+ macrophagesIL-10 activation. In Gut microbes, 14, 2145843. doi:10.1080/19490976.2022.2145843. https://pubmed.ncbi.nlm.nih.gov/36398889/

2. Raieli, Salvatore, Trichot, Coline, Korniotis, Sarantis, Pattarini, Lucia, Soumelis, Vassili. 2019. TLR1/2 orchestrate human plasmacytoid predendritic cell response to gram+ bacteria. In PLoS biology, 17, e3000209. doi:10.1371/journal.pbio.3000209. https://pubmed.ncbi.nlm.nih.gov/31017904/

3. Noreen, Mamoona, Arshad, Muhammad. . Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility. In Immunologic research, 62, 234-52. doi:10.1007/s12026-015-8640-6. https://pubmed.ncbi.nlm.nih.gov/25784622/

4. Huang, Kevin Chih-Yang, Ke, Tao-Wei, Chen, Jia-Yi, Chen, William Tzu-Liang, Chao, K S Clifford. 2023. Dysfunctional TLR1 reduces the therapeutic efficacy of chemotherapy by attenuating HMGB1-mediated antitumor immunity in locally advanced colorectal cancer. In Scientific reports, 13, 19440. doi:10.1038/s41598-023-46254-1. https://pubmed.ncbi.nlm.nih.gov/37945630/