Eicosanoid mediation of immune responses at early bacterial infection stage and its inhibition by Photorhabdus temperata subsp. temperata, an entomopathogenic bacterium

2018 ◽  
Vol 99 (4) ◽  
pp. e21502 ◽  
Author(s):  
Hyoil Kim ◽  
Duyeol Choi ◽  
Jihyeon Jung ◽  
Yonggyun Kim
2012 ◽  
Vol 78 (11) ◽  
pp. 3816-3823 ◽  
Author(s):  
Samyeol Seo ◽  
Sunghong Lee ◽  
Yongpyo Hong ◽  
Yonggyun Kim

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.


2011 ◽  
Vol 12 (9) ◽  
pp. 861-869 ◽  
Author(s):  
Feng Ma ◽  
Sheng Xu ◽  
Xingguang Liu ◽  
Qian Zhang ◽  
Xiongfei Xu ◽  
...  

Blood ◽  
2020 ◽  
Author(s):  
Xinyu Yang ◽  
Xiaoye Cheng ◽  
Yiting Tang ◽  
Xianhui Qiu ◽  
Zhongtai Wang ◽  
...  

Bacterial infection not only stimulates innate immune responses but also activates the coagulation cascades. Over-activation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC through amplifying the release of high mobility box group box 1 (HMGB1) into the blood stream. Inhibition of the expression of type 1 IFNs, disruption of their receptor IFN-α/βR or downstream effector (e.g., HMGB1) uniformly decreased Gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the pro-coagulant activity of tissue factor (TF) by promoting the externalization of phosphatidylserine (PS) to the outer cell surface, where PS assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-24-SCI-24
Author(s):  
Mark J. Miller

Abstract Cell-mediated immune responses are highly dependent on environmental context, thus making in vivo studies an important complement to in vitro and molecular approaches. Two-photon microscopy (2PM) is a fluorescence based imaging approach that allows single-cell dynamics to be studied directly in their 3D native tissue context. 2PM is an ideal approach for analyzing leukocyte trafficking dynamics quantitatively and testing cellular immune mechanisms in vivo. Several example applications will be presented where 2PM has uncovered novel immunological phenomena and provided fresh insight into immune responses to infection, autoimmunity and cancer. While 2P imaging has been used extensively to study immune cell trafficking and function in mice, progress is being made to use this imaging technique on clinical biopsy specimens to acquire a multi-dimensional picture of human tissue pathology. We used in vivo 2PM in pre-clinical models of arthritis and bacterial infection to compare and contrast the role of monocytes on neutrophil recruitment. The rapid recruitment of neutrophils and monocytes is critical to early host immune responses to bacterial infection. However, leukocyte recruitment also contributes to chronic inflammatory diseases such as human rheumatoid arthritis. Understanding how cell recruitment is regulated in different inflammatory contexts is crucial for developing safe and effective anti-inflammatory therapies. We found that monocyte depletion with clodronate-liposomes prevented arthritis development in a modified K/BxN serum transfer arthritis model. This protective effect was associated with significantly reduced neutrophil transendothelial migration efficiency. Furthermore, single-cell tracking of a minor population of extravasated neutrophils showed that neutrophil migration and chemotaxis in interstitial tissues was disrupted, contributing to decreased cell localization at phalangeal joints. Similar results were obtained when CCR2+ monocytes were depleted selectively using the monoclonal antibody MC-21, thus implicating CCR2+ monocytes as key regulators of neutrophil extravasation during arthritis initiation. In contrast, neutrophil recruitment to subcutaneous bacterial challenge remained intact and neutrophil extravasation and chemotaxis to sites of infection was not significantly different as compared to non-depleted controls. We also examined whether neutrophil extravasation during acute pulmonary inflammation required monocytes. Neutrophil recruitment in vivo was assessed in a mouse lung transplant-mediated ischemia reperfusion injury model. Similar to the results in the arthritis model, neutrophil recruitment in response to ischemia reperfusion injury was also monocyte dependent. In addition, Ccr2 knockout recipient mice were protected for ischemia reperfusion injury. Results from these complementary mouse models implicate CCR2+ monocytes as key regulators of neutrophil extravasation and chemotaxis in under conditions of aseptic inflammation and further suggest that the cell recruitment signals that that operate during bacterial infection may be quantitatively and/or qualitatively distinct. These studies raise the intriguing possibility that targeting monocytes during chronic inflammatory diseases such as rheumatoid arthritis or acute inflammatory conditions such as ischemia reperfusion injury might provide safer and more selective anti-inflammatory therapies than those that target neutrophils directly. Disclosures: No relevant conflicts of interest to declare.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Fangui Min ◽  
Lifang He ◽  
Yinzhu Luo ◽  
Shuwu Huang ◽  
Jinchun Pan ◽  
...  

To profile the dynamic changes of immune responses forM. kansasiiinfection, 3 cynomolgus monkeys were experimentally infected withM. kansasiiby intratracheal inhalation of 1 × 106 CFU bacteria per monkey. Every 2 to 4 weeks, tuberculin skin testings (TSTs) were performed and blood samples were collected for immunoassay. Multiple cytokines in a single sample were measured by Luminex xMAP technologies. IgM and IgA were detected by double-antibody sandwich ELISA. IgG against PPD and 11M. tuberculosisproteins were detected by using of indirect ELISA. At week 16, all animals were euthanized for necropsy and histological analysis. Positivities of TSTs emerged from week 2 to 6 postinfection. Leukocyte counts and T lymphocyte subsets experienced moderate increases. Among 44 kinds of cytokines, 36 kinds of them showed increases of different dynamic types and 8 kinds of them showed no specific changes. Total IgM and IgA showed a transient increase at an early infection stage. Positivities ofM. tuberculosisspecific IgM and IgA emerged as early as week 2 postinfection. All animals showed positive IgG against PPD and negative IgG responses to 38 kDa, MPT64L, TB16.3, 16 kDa, U1, and MTB81 antigens during the infection period. IgG against ESAT-6, CFP10, CFP10-ESAT-6, Ag85b, and 14 kDa antigens reached positive levels. The IgG avidities of PPD, ESAT-6, CFP10-ESAT-6, and Ag85b were all above 50 percent. In conclusion, the data indicate thatM. kansasiiinfection in monkeys can induce positivities of TSTs, increases of multiple cytokines, and cross-reactive antibody responses toM. tuberculosisantigens.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84481 ◽  
Author(s):  
Laura E. Crotty Alexander ◽  
Brenda J. Marsh ◽  
Anjuli M. Timmer ◽  
Ann E. Lin ◽  
Kayvan Zainabadi ◽  
...  

2007 ◽  
Vol 221 (3) ◽  
pp. 306-319 ◽  
Author(s):  
Jenny R. Roberts ◽  
Shih-Houng Young ◽  
Vincent Castranova ◽  
James M. Antonini

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