Abstract
The Toll-like receptor (TLR)-mediated NF-κB pathway is tightly controlled because overactivation may result in severe damage to the host, such as in the case of chronic inflammatory diseases and cancer. In mammals, sterile-alpha and armadillo motif-containing protein (SARM) plays an important role in negatively regulating this pathway. While Caenorhabditis elegans SARM is crucial for an efficient immune response against bacterial and fungal infections, it is still unknown whether Drosophila SARM participates in immune responses. Here, Litopenaeus vannamei SARM (LvSARM) was cloned and functionally characterized. LvSARM shared signature domains with and exhibited significant similarities to mammalian SARM. Real-time quantitative PCR analysis indicated that the expression of LvSARM was responsive to Vibrio alginolyticus and white spot syndrome virus (WSSV) infections in the hemocyte, gill, hepatopancreas and intestine. In Drosophila S2 cells, LvSARM was widely distributed in the cytoplasm and could significantly inhibit the promoters of the NF-κB pathway-controlled antimicrobial peptide genes (AMPs). Silencing of LvSARM using dsRNA-mediated RNA interference increased the expression levels of Penaeidins and antilipopolysaccharide factors, which are L.vannamei AMPs, and increased the mortality rate after V. alginolyticus infection. Taken together, our results reveal that LvSARM may be a novel component of the shrimp Toll pathway that negatively regulates shrimp AMPs, particularly Penaeidins and antilipopolysaccharide factors.
Highlights
Innate immunity is the body’s first line of defense against pathogens [1,2]. This immune response relies on germ lineencoded pattern recognition receptors (PRRs), such as the Tolllike receptors (TLRs), which participate in the recognition of pathogen-associated molecular patterns (PAMPs) [1,2]
Various PAMPs derived from viruses, bacteria, fungi and protozoa can be detected by distinct TLRs, leading to the activation of NF-kB [3]
In comparison with CeSARM, CrSARM and DmSARM, Litopenaeus vannamei SARM (LvSARM) is shorter in length and more similar to HsSARM (Fig. Schneider 2 (S2))
Summary
Innate immunity is the body’s first line of defense against pathogens [1,2]. This immune response relies on germ lineencoded pattern recognition receptors (PRRs), such as the Tolllike receptors (TLRs), which participate in the recognition of pathogen-associated molecular patterns (PAMPs) [1,2]. Various PAMPs derived from viruses, bacteria, fungi and protozoa can be detected by distinct TLRs, leading to the activation of NF-kB [3] This transcription factor has a central role in coordinating the expression of proinflammatory cytokines and chemokines to eliminate microbial infection by provoking inflammation and recruiting innate and adaptive immune cells [3,4]. The recognition of Grampositive bacteria and fungi by peptidoglycan recognition proteins (PGRPs) and Gram-negative bacteria-binding proteins (GNBPs), but not by Toll itself, triggers a proteolytic cascade that cleaves the endogenous Toll ligand Spatzle This ligand binds to the Toll receptor, leading to activation of the NF-kB family protein Dorsal [5,6]. No component of the Drosophila Toll pathway has been identified for the detection of viruses, certain viruses can activate the Toll-Dorsal pathway and induce AMP expression [5,7,8,9]
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