Hemolymph protease-5 links the melanization and Toll immune pathways in the tobacco hornworm,
            <i>Manduca sexta</i>

Wang, Yan; Yang, Fan; Cao, Xiaolong; Zou, Zhen; Lu, Zhiqiang; Kanost, Michael R.; Jiang, Haobo

doi:10.1073/pnas.2004761117

Cited by 39 publications

(55 citation statements)

References 46 publications

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“…Recognition of pathogens or parasites activates serine proteases, enzymes in hemolymph that activate PPOs into POs by proteolytic cleavage. POs launch a train of serine protease activation reactions that lead to synthesis of melanin, an important component of insect immunity [ 60 ]. Melanin can be deposited on newly formed hemocyte nodules and on parasites after hemocyte encapsulation, where, as a chemically active compound, it helps kill pathogens.…”

Section: Eicosanoid Actions In Insect Immunitymentioning

confidence: 99%

Eicosanoid Signaling in Insect Immunology: New Genes and Unresolved Issues

Kim

Stanley

2021

Genes

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This paper is focused on eicosanoid signaling in insect immunology. We begin with eicosanoid biosynthesis through the actions of phospholipase A2, responsible for hydrolyzing the C18 polyunsaturated fatty acid, linoleic acid (18:2n-6), from cellular phospholipids, which is subsequently converted into arachidonic acid (AA; 20:4n-6) via elongases and desaturases. The synthesized AA is then oxygenated into one of three groups of eicosanoids, prostaglandins (PGs), epoxyeicosatrienoic acids (EETs) and lipoxygenase products. We mark the distinction between mammalian cyclooxygenases and insect peroxynectins, both of which convert AA into PGs. One PG, PGI2 (also called prostacyclin), is newly discovered in insects, as a negative regulator of immune reactions and a positive signal in juvenile development. Two new elements of insect PG biology are a PG dehydrogenase and a PG reductase, both of which enact necessary PG catabolism. EETs, which are produced from AA via cytochrome P450s, also act in immune signaling, acting as pro-inflammatory signals. Eicosanoids signal a wide range of cellular immune reactions to infections, invasions and wounding, including nodulation, cell spreading, hemocyte migration and releasing prophenoloxidase from oenocytoids, a class of lepidopteran hemocytes. We briefly review the relatively scant knowledge on insect PG receptors and note PGs also act in gut immunity and in humoral immunity. Detailed new information on PG actions in mosquito immunity against the malarial agent, Plasmodium berghei, has recently emerged and we treat this exciting new work. The new findings on eicosanoid actions in insect immunity have emerged from a very broad range of research at the genetic, cellular and organismal levels, all taking place at the international level.

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Section: Eicosanoid Actions In Insect Immunitymentioning

confidence: 99%

Eicosanoid Signaling in Insect Immunology: New Genes and Unresolved Issues

Kim

Stanley

2021

Genes

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“…In insects, Toll receptor is activated by binding to its ligand, Spätzle, which is activated by sequential activation of serine proteases after pathogen recognition [19]. This led us to pose a PLOS PATHOGENS hypothesis that DSP1 acts as an initial immune inducer by activating the Toll-Spätzle signal pathway to activate PLA 2 .…”

Section: Introductionmentioning

confidence: 99%

Immune mediation of HMG-like DSP1 via Toll-Spätzle pathway and its specific inhibition by salicylic acid analogs

2021

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Xenorhabdus hominickii, an entomopathogenic bacterium, inhibits eicosanoid biosynthesis of target insects to suppress their immune responses by inhibiting phospholipase A2 (PLA2) through binding to a damage-associated molecular pattern (DAMP) molecule called dorsal switch protein 1 (DSP1) from Spodoptera exigua, a lepidopteran insect. However, the signalling pathway between DSP1 and PLA2 remains unknown. The objective of this study was to determine whether DSP1 could activate Toll immune signalling pathway to activate PLA2 activation and whether X. hominickii metabolites could inhibit DSP1 to shutdown eicosanoid biosynthesis. Toll-Spätzle (Spz) signalling pathway includes two Spz (SeSpz1 and SeSpz2) and 10 Toll receptors (SeToll1-10) in S. exigua. Loss-of-function approach using RNA interference showed that SeSpz1 and SeToll9 played crucial roles in connecting DSP1 mediation to activate PLA2. Furthermore, a deletion mutant against SeToll9 using CRISPR/Cas9 abolished DSP1 mediation and induced significant immunosuppression. Organic extracts of X. hominickii culture broth could bind to DSP1 at a low micromolar range. Subsequent sequential fractionations along with binding assays led to the identification of seven potent compounds including 3-ethoxy-4-methoxyphenol (EMP). EMP could bind to DSP1 and prevent its translocation to plasma in response to bacterial challenge and suppress the up-regulation of PLA2 activity. These results suggest that X. hominickii inhibits DSP1 and prevents its DAMP role in activating Toll immune signalling pathway including PLA2 activation, leading to significant immunosuppression of target insects.

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“…Phylogenetic analysis showed that O. furnacalis serpin–4 clustered together with B. mori serpin–4, M. sexta serpin–4, Operophtera brumata serpin–4 and Plutella xylostella serpin–4, with the bootstrap value of 100 ( Figure S4 ). Among them, M. sexta serpin–4 has been verified experimentally to inhibit PPO activation by inhibiting at least 4 target serine proteases ( 27 , 45 ). Therefore, we predicted that O. furnacalis serpin–4 could also function as an inhibitor of melanization response.…”

Section: Resultsmentioning

confidence: 99%

Serpin–4 Facilitates Baculovirus Infection by Inhibiting Melanization in Asian Corn Borer, Ostrinia furnacalis (Guenée)

Shen

Zhang

et al. 2022

Front. Immunol.

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Phenoloxidase (PO)–catalyzed melanization is a vital immune response in insects for defense against pathogen infection. This process is mediated by clip domain serine proteases and regulated by members of the serpin superfamily. We here revealed that the infection of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) significantly inhibited the PO activity in Ostrinia furnacalis hemolymph and induced the expression of O. furnacalis serpin–4. Addition of recombinant serpin-4 protein to O. furnacalis hemolymph resulted in a great increase of AcMNPV copies. Serpin-4 significantly suppressed the PO activity and the amidase activity in cleaving colorimetric substrate IEARpNA (IEARase activity) of hemolymph. Further experiments indicated it formed covalent complexes with three serine proteases (SP1, SP13 and SP105) and prevented them from cleaving their cognate downstream proteases in vitro. Altogether, O. furnacalis melanization restricted AcMNPV replication and serpin-4 facilitated AcMNPV infection by inhibiting serine proteases, SP1, SP13, and SP105 which were all involved in the melanization response.

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Hemolymph protease-5 links the melanization and Toll immune pathways in the tobacco hornworm, Manduca sexta

Cited by 39 publications

References 46 publications

Eicosanoid Signaling in Insect Immunology: New Genes and Unresolved Issues

Eicosanoid Signaling in Insect Immunology: New Genes and Unresolved Issues

Immune mediation of HMG-like DSP1 via Toll-Spätzle pathway and its specific inhibition by salicylic acid analogs

Serpin–4 Facilitates Baculovirus Infection by Inhibiting Melanization in Asian Corn Borer, Ostrinia furnacalis (Guenée)

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