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Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis

Despite their protective antimicrobial function, neutrophil extracellular traps (NETs) have been implicated in propagation of inflammatory responses in several disease conditions including sepsis. Highly diffusible exogenous ROS produced under such inflammatory conditions, can induce exuberant NETs,...

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Autores principales: Chauhan, Arun, Sharma, Atul, Tripathi, Jitendra K., Sun, Yuyang, Sukumran, Pramod, Singh, Brij B., Mishra, Bibhuti B., Sharma, Jyotika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209178/
https://www.ncbi.nlm.nih.gov/pubmed/34135384
http://dx.doi.org/10.1038/s41598-021-92001-9
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author Chauhan, Arun
Sharma, Atul
Tripathi, Jitendra K.
Sun, Yuyang
Sukumran, Pramod
Singh, Brij B.
Mishra, Bibhuti B.
Sharma, Jyotika
author_facet Chauhan, Arun
Sharma, Atul
Tripathi, Jitendra K.
Sun, Yuyang
Sukumran, Pramod
Singh, Brij B.
Mishra, Bibhuti B.
Sharma, Jyotika
author_sort Chauhan, Arun
collection PubMed
description Despite their protective antimicrobial function, neutrophil extracellular traps (NETs) have been implicated in propagation of inflammatory responses in several disease conditions including sepsis. Highly diffusible exogenous ROS produced under such inflammatory conditions, can induce exuberant NETs, thus making inhibition of NETs desirable in inflammatory diseases. Here we report that helminth parasite excretory/secretory factors termed as parasitic ligands (PL) inhibit ROS-induced NETs by blocking the activation of nonselective calcium permeable channel Transient Receptor Potential Melastatin 2 (TRPM2). Therapeutic implication of PL mediated blockage of NET formation was tested in preclinical model of septic peritonitis, where PL treatment regulated neutrophil cell death modalities including NET formation and mitigated neutrophil mediated inflammatory response. This translated into improved survival and reduced systemic and local bacterial load in infected mice. Overall, our results posit PL as an important biological regulator of neutrophil functions with implications to a variety of inflammatory diseases including peritonitis.
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spelling pubmed-82091782021-06-17 Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis Chauhan, Arun Sharma, Atul Tripathi, Jitendra K. Sun, Yuyang Sukumran, Pramod Singh, Brij B. Mishra, Bibhuti B. Sharma, Jyotika Sci Rep Article Despite their protective antimicrobial function, neutrophil extracellular traps (NETs) have been implicated in propagation of inflammatory responses in several disease conditions including sepsis. Highly diffusible exogenous ROS produced under such inflammatory conditions, can induce exuberant NETs, thus making inhibition of NETs desirable in inflammatory diseases. Here we report that helminth parasite excretory/secretory factors termed as parasitic ligands (PL) inhibit ROS-induced NETs by blocking the activation of nonselective calcium permeable channel Transient Receptor Potential Melastatin 2 (TRPM2). Therapeutic implication of PL mediated blockage of NET formation was tested in preclinical model of septic peritonitis, where PL treatment regulated neutrophil cell death modalities including NET formation and mitigated neutrophil mediated inflammatory response. This translated into improved survival and reduced systemic and local bacterial load in infected mice. Overall, our results posit PL as an important biological regulator of neutrophil functions with implications to a variety of inflammatory diseases including peritonitis. Nature Publishing Group UK 2021-06-16 /pmc/articles/PMC8209178/ /pubmed/34135384 http://dx.doi.org/10.1038/s41598-021-92001-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chauhan, Arun
Sharma, Atul
Tripathi, Jitendra K.
Sun, Yuyang
Sukumran, Pramod
Singh, Brij B.
Mishra, Bibhuti B.
Sharma, Jyotika
Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
title Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
title_full Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
title_fullStr Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
title_full_unstemmed Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
title_short Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
title_sort helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209178/
https://www.ncbi.nlm.nih.gov/pubmed/34135384
http://dx.doi.org/10.1038/s41598-021-92001-9
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