The recognition of pathogen-associated molecular patterns is accomplished by the recognition modules of pattern recognition receptors (PRRs). Leucine-rich repeats (LRRs) and C-type lectin-like domain (CTLD) represent the two most universal categories of recognition modules. In the current study, we identified a novel soluble and bacteria-inducible PRR comprising LRRs and a CTLD from the hepatopancreas of kuruma shrimp Marsupenaeus japonicus and named it Leulectin. The module arrangement of Leulectin is unique among all organisms. Both modules, together with the whole molecule, protected shrimp against Vibrio infection. By screening the pathogen-associated molecular patterns that shrimp might encounter, Leulectin was found to sense Vibrio flagellin through the LRRs and to recognize LPS through CTLD. The LRR-flagellin interaction was confirmed by pull-down and far-Western assays and was found to rely on the fourth LRR of Leulectin and the N terminus of flagellin. The recognition of LPS was determined by the long loop region of CTLD in a calcium-independent manner. By sensing the flagellin, LRRs could prevent its attachment to shrimp cells, thereby inhibiting Vibrio colonization. With the ability to recognize LPS, CTLD could agglutinate the bacteria and promote hemocytic phagocytosis. Our study clearly showed the division of labor and the synergy between different recognition modules and provided new insights into the concept of pattern recognition and the function of soluble PRRs in the antibacterial response.,Copyright © 2017 by The American Association of Immunologists, Inc.