Influence of Hyperproteinemia on Insect Innate Immune Function of the Circulatory System in Bombyx mori

SIMPLE SUMMARY: Hyperproteinemia, a condition of elevated protein levels in the blood, is associated with a diverse range of human and animal diseases. However, there is no reliable hyperproteinemia disease models or modeling methods in mammal or other organisms, and the effect of hyperproteinemia on immunity is still unknown. Our work succeeded in constructing an animal model of hyperproteinemia with no primary disease effects and a controllable plasma protein concentration (PPC) in an invertebrate model organism, Bombyx mori. Our work confirmed that high PPC enhances hemolymph phagocytosis via a rapid increase in granulocytes and inhibited hemolymph melanization due to inhibition of the prophenoloxidase (PPO) signaling pathway, and also upregulated the gene expression of antimicrobial peptides via activating the Toll and Imd pathways in NF-κB signaling, and showed an inconsistent antibacterial activity for Gram-positive and Gram-negative bacteria. Our results show that high PPC had multiple significant effects on the innate immune function of the silkworm circulatory system and is expected to be improved by endocrine hormones. Our work explores the pathogenesis of hyperproteinemia in an invertebrate model, and expands the scope for silkworm biomedical applications, even use for a potential drug development platform. ABSTRACT: Metabolic disorders of the circulatory system of animals (e.g., hyperglycemia and hyperlipidemia) can significantly affect immune function; however, since there is currently no reliable animal model for hyperproteinemia, its effects on immunity remain unclear. In this study, we established an animal model for hyperproteinemia in an invertebrate silkworm model, with a controllable plasma protein concentration (PPC) and no primary disease effects. We evaluated the influence of hyperproteinemia on innate immunity. The results showed that high PPC enhanced hemolymph phagocytosis via inducing a rapid increase in granulocytes. Moreover, while oenocytoids increased, the plasmacytes quickly dwindled. High PPC inhibited hemolymph melanization due to decreased phenoloxidase (PO) activity in the hemolymph via inhibiting the expression of the prophenoloxidase-encoding genes, PPO1 and PPO2. High PPC upregulated the gene expression of antimicrobial peptides via differential activation of the Toll and Imd signaling pathways associated with NF-κB signaling, followed by an induction of inconsistent antibacterial activity towards Gram-positive and Gram-negative bacteria in an animal model of high PPC. Therefore, high PPC has multiple significant effects on the innate immune function of the silkworm circulatory system.