CD206, also known as the mannose receptor or MRC1, is a specialized protein found on the surface of certain cells in the body. As a receptor, it binds to specific molecules. It belongs to the C-type lectin family, which recognizes various carbohydrate structures. CD206 plays a role in the body’s immune system, acting as a recognition point for certain substances.
Where CD206 is Found and What it Does
CD206 is primarily found on the surface of several immune cells, including macrophages, immature dendritic cells, and specialized endothelial cells in the liver and lymphatic system. It is also expressed on skin cells like human dermal fibroblasts and keratinocytes. This receptor is a transmembrane glycoprotein, spanning the cell membrane.
The main function of CD206 is to recognize and internalize specific carbohydrate structures, particularly those containing mannose, N-acetylglucosamine, and fucose. These sugars are often found on the surfaces of various microorganisms, such as bacteria, fungi, and viruses. By binding to these sugars, CD206 acts as a pattern recognition receptor, identifying foreign invaders.
Upon binding to these pathogens, CD206 facilitates their uptake into the cell through phagocytosis. Once internalized, the pathogens are transported to lysosomes for degradation. CD206 also plays a role in antigen presentation by immature dendritic cells. It internalizes mannosylated antigens, delivering them to compartments where they are loaded onto MHC molecules for presentation to T cells, influencing the adaptive immune response.
How CD206 Influences Health and Disease
CD206’s functions have broad implications for human health and disease. It plays a part in protective immune responses against certain infections, for instance, interacting with mannan-coated cell walls of microorganisms like Mycobacterium tuberculosis.
However, CD206’s role is not always protective; its altered expression or activity can contribute to disease pathology. In chronic inflammation, for example, increased levels of a soluble form of CD206 in the bloodstream have been linked to the severity of inflammatory diseases. This soluble form can even directly promote pro-inflammatory activation of macrophages.
In cancer, CD206 is highly expressed on tumor-associated macrophages (TAMs), particularly the M2 macrophage subtype, which are often associated with tumor progression. These CD206-expressing macrophages can contribute to tumor immunosuppression, metastasis, and the formation of new blood vessels that feed the tumor. High CD206 expression on tumor-associated macrophages is often associated with a worse prognosis in various solid cancers, including hepatocellular carcinoma and gastric cancers.
CD206-positive macrophages have also been implicated in fibrosis, such as in chronic liver disease. In highly fibrotic livers, there is a greater density of CD206-positive macrophages that produce pro-inflammatory molecules like TNFα and GM-CSF. This suggests these macrophages may contribute to chronic liver disease.
CD206 in Diagnosis and Treatment
CD206 serves as a biomarker for identifying specific cell types and disease states, particularly in immune-related disorders and cancer. It is a useful marker for M2 macrophages, a subtype involved in anti-inflammatory responses, tissue repair, and tumor progression. The presence of CD206-expressing macrophages provides insights into the immune microenvironment within a tumor or inflamed tissue.
In liver cancer, CD206 expression has been observed in cancer cells themselves, not just on associated immune cells. Its upregulation in liver cancer tissue compared to healthy tissue suggests it could be a biomarker for predicting disease occurrence and progression. Silencing CD206 in liver cancer cell lines has been shown to significantly decrease cell migration and invasion, indicating its role in tumor motility and invasiveness.
CD206 also holds promise as a target for therapeutic interventions. Strategies optimizing CD206-mediated uptake by macrophages are being explored for diagnosing and treating chronic infectious diseases. In cancer, therapies that selectively target CD206 on tumor-associated macrophages are being investigated to re-establish anti-tumor immune responses. For instance, certain synthetic compounds can induce a conformational change in CD206 on TAMs, leading to a reduction in immunosuppressive M2-like TAMs and an improvement in anti-tumor immunity.
Noninvasive imaging of CD206-positive M2 macrophages has also been successfully investigated as an early biomarker for post-chemotherapy tumor relapse and lymph node metastasis. Increased recruitment of CD206-positive M2 macrophages into tumors after chemotherapy suggests they could predict tumor relapse. This highlights CD206’s potential as a diagnostic marker and a guide for tailoring oncological therapies and assessing treatment response.