scholarly journals Immunosuppressive Activities of Novel PLA2 Inhibitors from Xenorhabdus hominickii, an Entomopathogenic Bacterium

Insects ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 505 ◽  
Author(s):  
Md. Mahi Imam Mollah ◽  
Aman Dekebo ◽  
Yonggyun Kim
Keyword(s):  
Immune Responses ◽  
Culture Broth ◽  
Dependent Manner ◽  
Bacterial Metabolites ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Lepidopteran Insect ◽  
Inhibitory Activities ◽  
Main Components ◽  
Ethylhexyl Phthalate

Eicosanoids mediate both cellular and humoral immune responses in insects. Phospholipase A2 (PLA2) catalyzes the first committed step in eicosanoid biosynthesis. It is a common pathogenic target of two entomopathogenic bacteria, Xenorhabdus and Photorhabdus. The objective of this study was to identify novel PLA2 inhibitors from X. hominickii and determine their immunosuppressive activities. To identify novel PLA2 inhibitors, stepwise fractionation of X. hominickii culture broth and subsequent enzyme assays were performed. Eight purified fractions of bacterial metabolites were obtained. Gas chromatography and mass spectrometry (GC-MS) analysis predicted that the main components in these eight fractions were 2-cyanobenzoic acid, dibutylamine, 2-ethyl 1-hexanol, phthalimide (PM), dioctyl terephthalate, docosane, bis (2-ethylhexyl) phthalate, and 3-ethoxy-4-methoxyphenol (EMP). Their synthetic compounds inhibited the activity of PLA2 in hemocytes of a lepidopteran insect, Spodoptera exigua, in a dose-dependent manner. They also showed significant inhibitory activities against immune responses such as prophenoloxidase activation and hemocytic nodulation of S. exigua larvae, with PM and EMP exhibiting the most potent inhibitory activities. These immunosuppressive activities were specific through PLA2 inhibition because an addition of arachidonic acid, a catalytic product of PLA2, significantly rescued such suppressed immune responses. The two most potent compounds (PM and EMP) showed significant insecticidal activities after oral administration. When the compounds were mixed with Bacillus thuringiensis (Bt), they markedly increased Bt pathogenicity. This study identified eight PLA2 inhibitors from bacterial metabolites of X. hominickii and demonstrated their potential as novel insecticides.

scholarly journals Phospholipase A2Inhibitors Synthesized by Two Entomopathogenic Bacteria, Xenorhabdus nematophila and Photorhabdus temperata subsp. temperata

2012 ◽  
Vol 78 (11) ◽  
pp. 3816-3823 ◽  
Author(s):  
Samyeol Seo ◽  
Sunghong Lee ◽  
Yongpyo Hong ◽  
Yonggyun Kim
Keyword(s):  
Immune Responses ◽  
Diamondback Moth ◽  
Culture Broth ◽  
Xenorhabdus Nematophila ◽  
Phenoloxidase Activity ◽  
Bacterial Metabolites ◽  
Content Type ◽  
Entomopathogenic Bacteria ◽  
Inhibitory Activities ◽  
Photorhabdus Temperata

ABSTRACTThe entomopathogenic bacteriaXenorhabdus nematophilaandPhotorhabdus temperatasubsp.temperatasuppress insect immune responses by inhibiting the catalytic activity of phospholipase A2(PLA2), which results in preventing biosynthesis of immune-mediating eicosanoids. This study identified PLA2inhibitors derived from culture broths of these two bacteria. BothX. nematophilaandP. temperatasubsp.temperataculture broths possessed significant PLA2-inhibitory activities. Fractionation of these bacterial metabolites in the culture broths using organic solvent and subsequent chromatography purified seven potent PLA2inhibitors, three of which (benzylideneacetone [BZA], proline-tyrosine [PY], and acetylated phenylalanine-glycine-valine [FGV]) were reported in a previous study. Four other compounds (indole, oxindole,cis-cyclo-PY, andp-hydroxyphenyl propionic acid) were identified and shown to significantly inhibit PLA2.X. nematophilaculture broth contained these seven compounds, whileP. temperatasubsp.temperataculture broth contained three compounds (BZA, acetylated FGV, andcis-cyclo-PY). BZA was detected in the largest amount among these PLA2compounds in both bacterial culture broths. All seven bacterial metabolites also showed significant inhibitory activities against immune responses, such as phenoloxidase activity and hemocytic nodulation; BZA was the most potent. Finally, this study characterized these seven compounds for their insecticidal activities against the diamondback moth,Plutella xylostella. Even though these compounds showed relatively low toxicities to larvae, they significantly enhanced the pathogenicity ofBacillus thuringiensis. This study reports bacterial-origin PLA2inhibitors, which would be applicable for developing novel insecticides.

scholarly journals Prostaglandin catabolism in Spodoptera exigua, a lepidopteran insect

2020 ◽  
Author(s):  
Shabbir Ahmed ◽  
Yonggyun Kim
Keyword(s):  
Immune Responses ◽  
Spodoptera Exigua ◽  
Inflammatory Mediator ◽  
Late Phase ◽  
Bacterial Challenge ◽  
Expression Levels ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Lepidopteran Insect ◽  
Rnai Treatment

ABSTRACTSeveral prostaglandins (PGs) and PG-synthesizing enzymes have been identified from insects. PGs can mediate cellular and humoral immune responses. However, uncontrolled and prolonged immune responses might have adverse effects on survival. PG catabolism in insects has not been reported. Here, using a transcriptomic analysis, we predicted two PG-degrading enzymes, PG dehydrogenase (SePGDH) and PG reductase (SePGR), in Spodoptera exigua, a lepidopteran insect. SePGDH and SePGR expression levels were upregulated after immune challenge. However, their expression peaks occurred after those of PG biosynthesis genes such as PGE2 synthase or PGD2 synthase. Indeed, SePGDH and SePGR expression levels were upregulated after injection with PGE2 or PGD2. In contrast, such upregulated expression was not detected after injection with leukotriene B4, an eicosanoid inflammatory mediator. RNA interference (RNAi) using double-stranded RNAs specific to SePGDH or SePGR suppressed their expression levels. The RNAi treatment resulted in an excessive and fatal melanization of larvae even after a non-pathogenic bacterial infection. Phenoloxidase (PO) activity mediating the melanization in larval plasma was induced by bacterial challenge or PGE2 injection. Although the induced PO activity decreased after 8 h in control, larvae treated with dsRNAs specific to PG-degrading enzyme genes kept the high PO activities for a longer period compared to control larvae. These results suggest that SePGDH and SePGR are responsible for PG degradation at a late phase of immune responses.

scholarly journals Prostaglandin catabolism in Spodoptera exigua, a lepidopteran insect

2020 ◽  
Vol 223 (21) ◽  
pp. jeb233221 ◽  
Author(s):  
Shabbir Ahmed ◽  
Yonggyun Kim
Keyword(s):  
Immune Responses ◽  
Spodoptera Exigua ◽  
Inflammatory Mediator ◽  
Late Phase ◽  
Bacterial Challenge ◽  
Expression Levels ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Lepidopteran Insect ◽  
Rnai Treatment

ABSTRACTSeveral prostaglandins (PGs) and PG-synthesizing enzymes have been identified from insects. PGs mediate cellular and humoral immune responses. However, uncontrolled and prolonged immune responses might have adverse effects on survival. PG catabolism in insects has not been reported. Here, using a transcriptomic analysis, we predicted the presence of two PG-degrading enzymes, PG dehydrogenase (SePGDH) and PG reductase (SePGR), in Spodoptera exigua, a lepidopteran insect. SePGDH and SePGR expression levels were upregulated after immune challenge. However, their expression peaks occurred after those of PG biosynthesis genes, such as those encoding PGE2 synthase or PGD2 synthase. SePGDH and SePGR expression levels were upregulated after injection with PGE2 or PGD2. In contrast, such upregulated expression was not detected after injection with leukotriene B4, an eicosanoid inflammatory mediator. RNA interference (RNAi) using double-stranded RNAs specific to SePGDH or SePGR suppressed their expression levels. The RNAi treatment resulted in an excessive and fatal melanization of larvae even after a non-pathogenic bacterial infection. Phenoloxidase (PO) activity mediating the melanization in larval plasma was induced by bacterial challenge or PGE2 injection. Although the induced PO activity decreased after 8 h in control larvae, those treated with dsRNAs specific to PG-degrading enzyme genes kept a high PO activity for a longer period. These results suggest that SePGDH and SePGR are responsible for PG degradation at a late phase of the immune response.

Specific humoral immune responses in 12 cases of food sensitization to sesame seed

1997 ◽  
Vol 27 (11) ◽  
pp. 1285-1291 ◽  
Author(s):  
M. N. KOLOPP-SARDA ◽  
D. A. MONERET-VAUTRIN ◽  
B. GOBERT ◽  
G. KANNY ◽  
M. BRODSCHII ◽  
...  
Keyword(s):  
Immune Responses ◽  
Sesame Seed ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Food Sensitization

scholarly journals Humoral immune responses to AAV gene therapy in the ocular compartment

2021 ◽  
Author(s):  
Michael Whitehead ◽  
Andrew Osborne ◽  
Patrick Yu‐Wai‐Man ◽  
Keith Martin
Keyword(s):  
Gene Therapy ◽  
Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Intersection of Sex and Frailty in Humoral Immune Responses to Influenza Vaccine in Community-Dwelling Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 271-272
Author(s):  
Janna Shapiro ◽  
Helen Kuo ◽  
Rosemary Morgan ◽  
Huifen Li ◽  
Sabra Klein ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza A ◽  
Community Dwelling ◽  
Influenza Vaccines ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
High Dose ◽  
Humoral Immune ◽  
Humoral Immune Responses

Abstract Older adults bear the highest burden of severe disease and complications associated with seasonal influenza, with annual vaccination serving as the best option for protection. Variability in vaccine efficacy exists, yet the host factors that affect immune responses to inactivated influenza vaccines (IIV) are incompletely understood. We hypothesized that sex and frailty interact to affect vaccine-induced humoral responses among older adults. To test this hypothesis, community-dwelling adults above 75 years of age were recruited yearly, assessed for frailty (as defined by the Cardiovascular Health Study criteria), and vaccinated with the high-dose trivalent IIV. Humoral immune responses were evaluated via hemagglutination inhibition titers. The study began during the 2014-2015 influenza season, with yearly cohorts ranging from 76-163 individuals. A total of 617 vaccinations were delivered from 2014-2019. In preliminary analyses, the outcome of interest was seroconversion, defined as ≥ 4-fold rise in titers. Crude odds ratios suggest that females are more likely to seroconvert to influenza A strains (H1N1: OR = 1.39, (0.98-1.96) ; H3N2: 1.17 (0.85 – 1.62)), while males are more likely to seroconvert to the B strain (OR = 0.85 (0.60 – 1.22)). Furthermore, this sex difference was modified by frailty – for example, the odds of seroconversion to H1N1 were 65% higher for females than males among those who were nonfrail, and only 30% higher among females who were frail. Together, these results suggest that sex and frailty interact to impact immune responses to influenza vaccines. These findings may be leveraged to better protect vulnerable populations.

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