LECT2 Is a Novel Antibacterial Protein in Vertebrates

Abstract

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 LECT2 gene, two LECT2 genes exist in teleost fish, named LECT2-a and LECT2-b. Using grass carp as a research model, we found that the expression pattern of grass carp LECT2-a (gcLECT2-a) is more similar to that of LECT2 in tetrapods, while gcLECT2-b 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 Aeromonas hydrophila 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.

Comparative study on antibacterial characteristics of the multiple liver expressed antimicrobial peptides (LEAPs) in teleost fish

“…The membrane permeability of bacteria after the treatment of peptides was assessed by flow cytometry as previously described ( 33 ) with minor modifications. In brief, V. fluvialis WY91-24-3 were cultured to mid-logarithmic phase, then washed twice and resuspended to 10 6 CFU/ml with 10 mM NaPB (pH 7.4).…”

The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential

“…LECT2 was firstly found to be associated with bacterial and viral infection in multiple teleosts (63)(64)(65)(66). the anti-bacterial/antiviral roles of LECT2 have also been verified in Aves (67, 68), mammals (22,69), and human beings (23,70). In vertebrates, LECT2 was firstly considered to exhibit its anti-bacterial/anti-viral activities by activating immune cells (macrophages, heterophils, and lymphocytes) (22,68,71) and downregulating pro-inflammatory factors such as TNF-a and IL-6 (22,24).…”

“…LECT2 has also been found to shift the development of pro-inflammatoryTh1/Th17 cells to anti-inflammatory Treg cells via the differentiation of bone marrow-derived dendritic cells (BMDCs) into dendritic cells, secretion of inflammatory cytokines, and differentiation of T cells after Helicobacter pylori infection in a CD209a receptor-dependent manner, suggesting that interrupting the LECT2-CD209a interaction may provide a promising target for H. pylori clearance ( 72 ). Moreover, LECT2 has direct anti-bacterial activity in teleosts, and this activity is conserved among vertebrates apart from humans ( 69 ). Interestingly, although LECT2 has two copies in teleosts, only LECT2-b exhibits direct anti-bacterial activity in grass carp.…”

“…Mounting evidence supports that LECT2 has versatile roles in immune diseases. It attenuates tumorigenesis by modulating TIM (51,52); modulates inflammatory responses in several tissues such as liver (7,8,25,40,56,59), bone marrow (29), joints (30)(31)(32)(33), and blood vessels (13, 25-27); alleviates bacteria/virus-induced sepsis (22,23,42,(67)(68)(69)(70)(71); and accelerates the progression of allergic diseases (35,77). It also mediates the Wnt/b-catenin pathway to regulate osteogenic differentiation of MSCs (28).…”

IL-6 Mutation Attenuates Liver Injury Caused by Aeromonas hydrophila Infection by Reducing Oxidative Stress in Zebrafish

“…One il-6 −/− zebrafish group was injected intraperitoneally with a mixture of rDrIL-6 (1 µL per zebrafish, 10 ng/µL) and A. hydrophila (1 µL) and named the rDrIL-6 group. At the same time, rdrIL-6 was replaced with equal amounts of TrxA (labeled protein [54]) and PBS, which were named the TrxA group and KO-AH group, respectively. In addition, a group of WT zebrafish (n = 60) intraperitoneally injected with a mixture of PBS and A. hydrophila was named the WT-AH group.…”