Abstract
Peptidoglycan recognition protein (PGRP) is an important pattern recognition receptor in innate immunity that is vital for bacterial recognition and defense in insects. Few studies report the role of PGRP in viral infection. Here we cloned two forms of PGRP from the model lepidopteran Bombyx mori: BmPGRP2-1 is a transmembrane protein, whereas BmPGRP2-2 is an intracellular protein. BmPGRP2-1 bound to diaminopimelic acid (DAP)-type peptidoglycan (PGN) to activate the canonical immune deficiency (Imd) pathway. BmPGRP2-2 knockdown reduced B. mori nucleopolyhedrovirus (BmNPV) multiplication and mortality in cell lines and in silkworm larvae, while its overexpression increased viral replication. Transcriptome and quantitative PCR (qPCR) results confirmed that BmPGRP2 negatively regulated phosphatase and tensin homolog (PTEN). BmPGRP2-2 expression was induced by BmNPV, and the protein suppressed PTEN-phosphoinositide 3-kinase (PI3K)/Akt signaling to inhibit cell apoptosis, suggesting that BmNPV modulates BmPGRP2-2-PTEN-PI3K/Akt signaling to evade host antiviral defense. These results demonstrate that the two forms of BmPGRP2 have different functions in host responses to bacteria and viruses.
Highlights
Innate immunity is a self-defense mechanism against infectious non-self entities and is present in all metazoans [1, 2]
BmPGRP2-1 consisted of exons 1, 2, and 3 with a 242-bp 3′ untranslated region (UTR), whereas BmPGRP2-2 consisted of exons 1, 4, 5, 6, and 7 with a 224-bp 3′ UTR (Figure 1A)
We demonstrated that BmPGRP2-1 binds to diaminopimelic acid (DAP)-type PGN to activate immune deficiency (Imd) signaling and inhibit bacteria, whereas BmNPVinduced BmPGRP2-2 suppresses host cell apoptosis to enable viral replication
Summary
Innate immunity is a self-defense mechanism against infectious non-self entities and is present in all metazoans [1, 2]. The innate immune system of insects consists of humoral defenses that include the production of soluble effector molecules and cellular response like phagocytosis and encapsulation that are mediated by hemocytes [3]. The innate immune response is mediated by germline-encoded pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) that are present in pathogens but absent in the host [2, 4, 5]. PAMPs include b-glucan, lipopolysaccharides (LPS) of gram-negative (G–) bacteria, and peptidoglycans (PGNs) of both gram-positive (G+) and G– bacteria, as well as bacterial and viral DNA and RNA and related molecules [2, 4, 5].
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