CLEC5A (C-type lectin domain family 5 member A), also known as MDL-1. is a pattern recognition receptor (PRR) belonging to the C-type lectin family. It is primarily expressed on myeloid cells, including macrophages, neutrophils, and dendritic cells. CLEC5A recognizes pathogen-associated molecular patterns (PAMPs) from viruses, bacteria, and fungi, such as dengue virus, *Staphylococcus aureus*, and *Aspergillus fumigatus*. Upon ligand binding, CLEC5A associates with the adaptor protein DAP12 to activate downstream signaling pathways, including Syk kinase, leading to the production of pro-inflammatory cytokines (e.g., TNF-α, IL-6) and reactive oxygen species. While this response is critical for host defense, excessive CLEC5A activation can exacerbate inflammatory diseases, sepsis, or viral-induced cytokine storms.
CLEC5A-targeting antibodies have emerged as therapeutic tools to modulate immune responses. Antagonistic antibodies blocking CLEC5A-DAP12 interactions have shown potential in preclinical models to mitigate hyperinflammation in dengue infection, rheumatoid arthritis, and septic shock. Conversely, agonist antibodies may enhance pathogen clearance in immunocompromised conditions. Challenges remain in balancing efficacy and safety, as CLEC5A also plays roles in tissue homeostasis and cross-talk with other PRRs (e.g., TLRs). Current research focuses on optimizing antibody specificity and exploring combination therapies to harness CLEC5A's dual role in immunity and inflammation.