Role of a macrophage receptor with collagenous structure (MARCO) in regulating monocyte/macrophage functions in ayu, Plecoglossus altivelis.

Macrophage receptor with collagenous structure (MARCO) plays essential roles in phagocytic cell-mediated innate immune responses. However, studies regarding MARCO, especially its functions, are limited in teleost species. In this study, we identified a MARCO molecule (PaMARCO) from ayu (Plecoglossus altivelis). PaMARCO shared conserved functional domains with its mammalian counterparts. Sequence analysis showed that PaMARCO was most closely related to its rainbow trout (Oncorhynchus mykiss) counterpart. PaMARCO expression was upregulated in all tested immune tissues and monocytes/macrophages (MO/MΦ) upon Vibrio anguillarum infection, and blocking its function significantly decreased the immune responses of MO/MΦ during infection. PaMARCO could bind to the tested gram-positive and -negative bacteria in a Ca2+-dependent manner in vitro. Furthermore, the phagocytosis and bacterial killing activities of MO/MΦ were significantly decreased upon PaMARCO blockade using anti-PaMARCO IgG. PaMARCO was also involved in the polarization processes of ayu MO/MΦ. The upregulated expression of representative cytokines in LPS-induced M1 type (TNF-α, IL-1β) or cAMP-induced M2 type (TGF-β, IL-10) were inhibited in the anti-PaMARCO IgG-treated group, indicating that PaMARCO may be involved in the regulation of both inflammation priming and inflammation resolution of MO/MΦ. In conclusion, our results implicate that PaMARCO has essential regulatory roles for bacterial binding, clearance, and the polarization processes of ayu MO/MΦ.