Clec5a-KO Mouse

CLEC5A, a spleen tyrosine kinase (Syk)-coupled C-type lectin, is highly expressed by monocytes, macrophages, neutrophils, and dendritic cells. It acts as a pattern recognition receptor, binding to terminal fucose and mannose moieties of viral glycans, as well as N -acetylglucosamine (GlcNAc) and N -acetylmuramic acid (MurNAc) disaccharides of bacterial cell walls. CLEC5A mediates microbe-induced inflammatory responses via Syk activation and is thus crucial in both septic and aseptic inflammatory reactions [1].

In various disease models, CLEC5A has shown significant roles. In a mosquito-to-mouse ZIKV disease model, CLEC5A knockout mice (clec5a-/-stat1-/-) had reduced testicular ZIKV titer, local inflammation, neutrophil invasion, and improved spermatozoa function compared to ZIKV-infected stat1-/-mice, indicating its role in ZIKV-induced orchitis and oligospermia [2]. In SARS-CoV-2 studies, antagonistic mAbs against CLEC5A inhibited COVID-19-EVs-induced NET formation, and clec5a-/-/tlr2-/-mice had attenuated thromboinflammation, highlighting CLEC5A's role in SARS-CoV-2-induced lung inflammation [3]. In Pseudomonas aeruginosa-induced pneumonia, blockade of CLEC5A attenuated NETosis and lung injury, and co-administration of anti-CLEC5A mAb with ciprofloxacin increased the survival rate of mice challenged with a lethal dose of P. aeruginosa [4].

In conclusion, CLEC5A is a key pattern recognition receptor mediating microbe-induced inflammatory responses. Gene knockout mouse models have revealed its significant roles in viral-induced inflammatory diseases such as ZIKV-induced testicular damage, SARS-CoV-2-induced lung inflammation, and bacterial-induced acute lung injury, providing potential therapeutic targets for these diseases.

References:

1. Sung, Pei-Shan, Chang, Wei-Chiao, Hsieh, Shie-Liang. . CLEC5A: A Promiscuous Pattern Recognition Receptor to Microbes and Beyond. In Advances in experimental medicine and biology, 1204, 57-73. doi:10.1007/978-981-15-1580-4_3. https://pubmed.ncbi.nlm.nih.gov/32152943/

2. Wang, Hsin-Wei, Li, Hsing-Han, Wu, Shih-Cheng, Chen, Chun-Hong, Hsieh, Shie-Liang. 2023. CLEC5A mediates Zika virus-induced testicular damage. In Journal of biomedical science, 30, 12. doi:10.1186/s12929-023-00906-6. https://pubmed.ncbi.nlm.nih.gov/36803804/

3. Sung, Pei-Shan, Yang, Shao-Ping, Peng, Yu-Chun, Tao, Mi-Hwa, Hsieh, Shie-Liang. 2022. CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation. In Journal of biomedical science, 29, 52. doi:10.1186/s12929-022-00832-z. https://pubmed.ncbi.nlm.nih.gov/35820906/

4. Sung, Pei-Shan, Peng, Yu-Chun, Yang, Shao-Ping, Chiu, Cheng-Hsun, Hsieh, Shie-Liang. 2022. CLEC5A is critical in Pseudomonas aeruginosa-induced NET formation and acute lung injury. In JCI insight, 7, . doi:10.1172/jci.insight.156613. https://pubmed.ncbi.nlm.nih.gov/36048544/