LECT2 Is a Novel Antibacterial Protein in Vertebrates

• Published in: The Journal of immunology (1950) 2022-04, Vol.208 (8), p.2037-2053
• Main Authors: Hu, Ya-Zhen, Ma, Zi-You, Wu, Chang-Song, Wang, Jie, Zhang, Yong-An, Zhang, Xu-Jie
• Format: Article
• Language: English
• Subjects: Aeromonas hydrophila; Animals; Anti-Bacterial Agents; Carps - metabolism; Fish Diseases; Fish Proteins - genetics; Fish Proteins - metabolism; Gram-Negative Bacterial Infections; Immunity, Innate; Leukocytes - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2100812

In vertebrates, leukocyte-derived chemotaxin-2 (LECT2) is an important immunoregulator with conserved chemotactic and phagocytosis-stimulating activities to leukocytes during bacterial infection. However, whether LECT2 possesses direct antibacterial activity remains unknown. In this article, we show that, unlike tetrapods with a single gene, two genes exist in teleost fish, named and Using grass carp as a research model, we found that the expression pattern of grass carp ( ) is more similar to that of in tetrapods, while has evolved to be highly expressed in mucosal immune organs, including the intestine and skin. Interestingly, we found that gcLECT2-b, with conserved chemotactic and phagocytosis-stimulating activities, can also kill Gram-negative and Gram-positive bacteria directly in a membrane-dependent and a non-membrane-dependent manner, respectively. Moreover, gcLECT2-b could prevent the adherence of bacteria to epithelial cells through agglutination by targeting peptidoglycan and lipoteichoic acid. Further study revealed that gcLECT2-b can protect grass carp from infection in vivo, because it significantly reduces intestinal necrosis and tissue bacterial load. More importantly, we found that LECT2 from representative tetrapods, except human, also possesses direct antibacterial activities, indicating that the direct antibacterial property of LECT2 is generally conserved in vertebrates. Taken together, to our knowledge, our study discovered a novel function of LECT2 in the antibacterial immunity of vertebrates, especially teleost fish, greatly enhancing our knowledge of this important molecule.