In addition, Drosophila antiviral autophagy against vesicular stomatitis virus (VSV) is triggered by the Toll-7 receptor on the plasma membrane ( Nakamoto et al., 2012). Interestingly, recent studies have suggested that the Toll signaling pathway is also required for antiviral immune response against oral infection ( Ferreira et al., 2014). Moreover, an active form of the spätzle cytokine directly binds to the multimerized Toll receptors to initiate the intracellular Toll signaling pathway ( Weber et al., 2003 Hu et al., 2004). Further, it has been suggested that Gram-positive bacteria recognized by the peptidoglycan recognition protein (PGRP) activate the Drosophila Toll pathway ( Michel et al., 2001). In addition, the dorso-ventral regulatory gene cassette ( spätzle-Toll-cactus) is involved in the antifungal immune response by regulating the expression of the antifungal peptide gene drosomycin ( Lemaitre et al., 1996). In the Drosophila model, the dorsal gene, a homolog of a rel-related gene acting as a nuclear factor-kappa B (NF-κB), promotes expression of an antifungal peptide, diptericin, through a Toll signaling pathway, defined by Toll or cactus mutant screening ( Lemaitre et al., 1995). Since 1995, various research groups have studied the effects of the Toll signaling pathway on innate immune responses against various pathogens. The precursor form of the Toll receptor reportedly converts to an active Toll receptor in a position-dependent manner, relative to the dorsal-ventral axis ( Anderson et al., 1985). The Toll receptor was first identified in Drosophila melanogaster and was reported to be essential for establishment of the dorsal-ventral patterning in the Drosophila embryo. The Toll and immune deficiency (IMD) signaling pathways are the major immune responses that regulate the production of AMPs in Drosophila ( De Gregorio et al., 2002). AMP production is one of the most important innate immune responses. Innate immune responses, such as antimicrobial peptide (AMP) production, coagulation, prophenoloxidase cascade, phagocytosis, melanization, nodule formation, and encapsulation processes, are the major defense systems against invading pathogens in invertebrates. molitor innate immunity, causes the sequestration of Gram-negative bacteria by the regulatory action of antimicrobial peptides, and enhances the survival of T. These results indicate that TmSpz1b is involved in the T. coli challenge suggesting the relationship to Toll signaling pathway. Further, the TmDorX2 transcripts were downregulated in TmSpz1b silenced individuals upon E. In addition, RNAi-based functional assay characterized TmSpz1b to be involved in the positive regulation of antimicrobial peptide genes in hemocytes and fat bodies. TmSpz1b silenced larvae were significantly more susceptible to E. ![]() The mRNA expression of TmSpz1b was highly induced in the hemocytes after Escherichia coli, Staphylococcus aureus, and Candida albicans stimulation of T. TmSpz1b was mostly expressed in the hemocytes of T. A conserved cystine-knot domain with seven cysteine residues in TmSpz1b was involved in three disulfide bridges and the formation of a spätzle dimer. The 702 bp open reading frame of TmSpz1b encoded a putative protein of 233 amino acid residues. TmSpz1b was bioinformatically analyzed, and functionally characterized for the antimicrobial function by RNA interference (RNAi). In this study, we identified a novel Spätzle isoform ( TmSpz1b) from RNA sequencing database of Tenebrio molitor. ![]() In the Toll-NF-κB pathway, the extracellular spätzle protein acts as a downstream ligand for Toll receptors in insects. Unlike in the mammalian model, in the insect model, invading pathogens are recognized by extracellular receptors, which activate the Toll signaling pathway through an extracellular serine protease cascade. Innate immunity is the ultimate line of defense against invading pathogens in insects. ![]()
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