Review of the Role of Parasitic Nematode Excretory/Secretory Proteins in Host Immunomodulation

Okakpu, Ogadinma K.; Dillman, Adler R.

doi:10.1645/21-33

Cited by 16 publications

(11 citation statements)

References 94 publications

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“…In other words, the injection treatment bypasses the necessary length of time for the EPNs to manufacture and secrete the lethal dose. More interestingly, it has been shown that non-activated IJs have higher gene expression of 88 out of the 472 venom proteins compared to activated IJs, suggesting that these venomous proteins may be synthesized earlier during the host seeking stage and then quickly released following cuticular invasion when the parasites reach the insect hemolymph 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has begun to isolate and characterize some of the protein compounds within the S. carpocapsae ESP mixture to better understand the intricacies of how these individual components target specific insect host defenses 34 . Among the isolated molecules, different types of serine protease inhibitors (serpins) have been identified.…”

Section: Discussionmentioning

confidence: 99%

“…EPNs contain conserved orthologs which are maintained across vertebrate and human parasitic nematodes, rendering them ideal model organisms for conducting research in a safe and cost-effective manner to understand helminth-related diseases that negatively impact human health 30 , 32 , 34 . The aim of this research was to examine how the adult Drosophila immune system is modulated in response to S. carpocapsae ESPs and determine the pathogenic contributions of the isolated molecules.…”

Section: Introductionmentioning

confidence: 99%

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Excreted secreted products from the parasitic nematode Steinernema carpocapsae manipulate the Drosophila melanogaster immune response

Jones

Tafesh-Edwards

Kenney

et al. 2022

Sci Rep

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Steinernema carpocapsae is an entomopathogenic nematode (EPN) that rapidly infects and kills a wide range of insect hosts and has been linked to host immunosuppression during the initial stages of infection. The lethal nature of S. carpocapsae infections has previously been credited to its symbiotic bacteria; however, it has become evident that the nematodes are able to effectively kill their hosts independently through their excretion/secretion products (ESPs). Here we examined how the adult Drosophila melanogaster immune system is modulated in response to S. carpocapsae ESPs in an attempt to ascertain individual pathogenic contributions of the isolated compound. We found that the S. carpocapsae ESPs decrease the survival of D. melanogaster adult flies, they induce the expression of certain antimicrobial peptide-encoding genes, and they cause significant reduction in phenoloxidase enzyme activity and delay in the melanization response in males flies. We also report that S. carpocapsae ESPs affect hemocyte numbers in both male and female individuals. Our results indicate the manipulative role of EPN ESPs and reveal sex-specific differences in the host response against nematode infection factors. These findings are beneficial as they promote our understanding of the molecular basis of nematode pathogenicity and the parasite components that influence nematode-host interactions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Excreted secreted products from the parasitic nematode Steinernema carpocapsae manipulate the Drosophila melanogaster immune response

Jones

Tafesh-Edwards

Kenney

et al. 2022

Sci Rep

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“…Except for the tissue damage caused by the helminth infection in the parasitized host, the helminths themselves have also developed an immune evasion mechanism to reduce host immune attack as a survival strategy. This defense mechanism includes the secretion of functional molecules that play an immunomodulatory role in the host immune response [ 4 ]. As a result, the reduced immune response to the helminth infection may benefit the hosts themselves, with reduced immunopathology and less tissue damage caused by the infection [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages

Huang

Li²,

Zheng³

et al. 2023

TropicalMed

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Capillaria hepatica is a seriously neglected zoonotic parasite, which infects the liver of mammalian hosts, causing fibrosis or even hepatic failure. At present, the immune responses elicited by C. hepatica are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway in the context of C. hepatica-induced pathology are not known. In this study, we identify that the late stage of infection with C. hepatica—especially the egg-derived antigens—modulates the host immune responses to promote alternatively activated macrophage (M2) polarization and programmed death ligand 2 (PD-L2) expression. The PD-L2-expressing alternatively activated M2 macrophages play an important role in maintaining Th2-biased regulatory immune responses, which may facilitate the survival of parasitic worms or eggs within the infected liver and reduce the liver pathology caused by the egg granulomas. Treatment with anti-PD-L2 antibody had no effect on the survival of parasitic eggs but deteriorated the pathology of egg granulomas. The obtained results suggest that PD-1/PD-L2 signaling, which is involved in alternative macrophage polarization, determines the immune response pattern and the immunopathology, consequently determining the outcome of the parasitic infection.

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“…Characterization of individual proteins has remained challenging due to the technical obstacles of vertebrate model systems for testing hypotheses of potential effector proteins. Utilization of insect model systems however, has resulted in molecular characterization of individual proteins found in EPN ESPs ( 9 ). Due to the high homology EPN ESPs have with nematode parasites of vertebrates such as Strongyloides stercoralis , the molecular mechanisms of their ESPs are likely conserved ( 10 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

Parasitic nematode secreted phospholipase A2 suppresses cellular and humoral immunity by targeting hemocytes in Drosophila melanogaster

et al. 2023

Self Cite

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A key aspect of parasitic nematode infection is the nematodes’ ability to evade and/or suppress host immunity. This immunomodulatory ability is likely driven by the release of hundreds of excretory/secretory proteins (ESPs) during infection. While ESPs have been shown to display immunosuppressive effects on various hosts, our understanding of the molecular interactions between individual proteins released and host immunity requires further study. We have recently identified a secreted phospholipase A2 (sPLA2) released from the entomopathogenic nematode (EPN) Steinernema carpocapsae we have named Sc-sPLA2. We report that Sc-sPLA2 increased mortality of Drosophila melanogaster infected with Streptococcus pneumoniae and promoted increased bacterial growth. Furthermore, our data showed that Sc-sPLA2 was able to downregulate both Toll and Imd pathway-associated antimicrobial peptides (AMPs) including drosomycin and defensin, in addition to suppressing phagocytosis in the hemolymph. Sc-sPLA2 was also found to be toxic to D. melanogaster with the severity being both dose- and time-dependent. Collectively, our data highlighted that Sc-sPLA2 possessed both toxic and immunosuppressive capabilities.

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Review of the Role of Parasitic Nematode Excretory/Secretory Proteins in Host Immunomodulation

Cited by 16 publications

References 94 publications

Excreted secreted products from the parasitic nematode Steinernema carpocapsae manipulate the Drosophila melanogaster immune response

Excreted secreted products from the parasitic nematode Steinernema carpocapsae manipulate the Drosophila melanogaster immune response

PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages

Parasitic nematode secreted phospholipase A2 suppresses cellular and humoral immunity by targeting hemocytes in Drosophila melanogaster

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