Marco-KO Mouse

Marco, short for Macrophage receptor with collagenous structure, is a member of scavenger receptor class A (SR-A) [2]. It can trigger an immune response, playing a crucial role in bridging innate and adaptive immunity, eliminating pathogens, and has therapeutic potential as an immunotherapy target [2]. MARCO is involved in various signaling pathways such as TNF/NFκB, KRAS, PI3K/AKT/mTOR, IL-6-STAT3, TGFβ, and p53 pathways [1].

In the context of diseases, in liver, commensal bacteria induce Marco+ immunosuppressive macrophages that limit excessive inflammation at the liver's gateway; Marco-deficient conditions exacerbate inflammation in the periportal vein zones, and chronic liver diseases show decreased numbers of Marco+ macrophages [3]. In triple-negative breast cancer, a tumor-specific splicing variant MARCO-TST promotes tumor progression by interacting with PLOD2 and enhancing HIF-1α stability, forming a hypoxic tumor microenvironment [5]. In porcine reproductive and respiratory syndrome virus (PRRSV) infection, MARCO is a host restriction factor that inhibits the virus through intensifying virus-induced apoptosis [4].

In conclusion, Marco is essential in immune-related functions and pathogen clearance. Its role in various disease conditions like chronic liver diseases, breast cancer, and viral infections has been revealed through different research models. Understanding Marco can potentially provide new directions for immunotherapy and treatment strategies in these disease areas.

References:

1. Dong, Qingyu, Zhang, Shunhao, Zhang, Haotian, Wang, Guihua, Wang, Xudong. 2023. MARCO is a potential prognostic and immunotherapy biomarker. In International immunopharmacology, 116, 109783. doi:10.1016/j.intimp.2023.109783. https://pubmed.ncbi.nlm.nih.gov/36773567/

2. Zhou, Guiyuan, Zhang, Lei, Shao, Suxia. 2024. The application of MARCO for immune regulation and treatment. In Molecular biology reports, 51, 246. doi:10.1007/s11033-023-09201-x. https://pubmed.ncbi.nlm.nih.gov/38300385/

3. Miyamoto, Yu, Kikuta, Junichi, Matsui, Takahiro, Takeda, Kiyoshi, Ishii, Masaru. 2024. Periportal macrophages protect against commensal-driven liver inflammation. In Nature, 629, 901-909. doi:10.1038/s41586-024-07372-6. https://pubmed.ncbi.nlm.nih.gov/38658756/

4. Zhang, Xiaoxiao, Chen, Yongjie, Li, Songbei, Liu, Xiaohong, Guo, Chunhe. 2023. MARCO Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection through Intensifying Viral GP5-Induced Apoptosis. In Microbiology spectrum, 11, e0475322. doi:10.1128/spectrum.04753-22. https://pubmed.ncbi.nlm.nih.gov/37078873/

5. Yang, Yun-Song, Jin, Xi, Li, Qin, Huang, Shenglin, Shao, Zhi-Ming. 2022. Superenhancer drives a tumor-specific splicing variant of MARCO to promote triple-negative breast cancer progression. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2207201119. doi:10.1073/pnas.2207201119. https://pubmed.ncbi.nlm.nih.gov/36343244/