A Novel Ig Domain–Containing C-Type Lectin Triggers the Intestine–Hemocyte Axis to Regulate Antibacterial Immunity in Crab

Abstract

The C-type lectin family with the signature C-type lectin–like domain promotes antibacterial host defense within the animal kingdom. We examined the role of Chinese mitten crab, Eriocheir sinensis (H. Milne-Edwards) (Decapoda: Grapsidae) Ig domain–containing C-type lectin (EsIgLectin), a novel and poorly understood member of the C-type lectin family. EsIgLectin was expressed primarily by both hemocytes (E. sinensis) and intestines, with significantly induced mRNA expression on intestinal or hemolymph bacterial infections. As a soluble protein, both its C-type lectin–like domain and the Ig domain were required for bacterial binding, bacterial agglutination, bacterial growth inhibition, and in vivo bacterial clearance. Polymeric EsIgLectin could be constructed via the disulfide bond in the Ig domain, significantly enhancing EsIgLectin antibacterial activity. EsIgLectin promoted bacterial phagocytosis in an Ig domain–dependent manner in hemocytes, while it controlled microbial homeostasis and protected against bacteria-induced inflammation in the intestine. Protein interaction studies revealed that the EsIgLectin Ig domain bound to the first Ig domain of the polymeric Ig receptor, which was essential for EsIgLectin-induced bacterial phagocytosis. The temporal sequence of cell interactions during intestinal inflammation is only beginning to be understood. In this article, we show that hemocyte-derived EsIgLectin entered the intestinal wall at the later phase of intestinal inflammation. Moreover, EsIgLectin protected the host against intestinal and hemolymph infections in a polymeric Ig receptor–dependent manner. Therefore, the EsIgLectin promoted bacterial clearance and protected against inflammatory disease through an independent or synergistic effect of hemocytes and intestines in invertebrates.