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

Abstract 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 exuber...

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Autores principales:	Arun Chauhan, Atul Sharma, Jitendra K. Tripathi, Yuyang Sun, Pramod Sukumran, Brij B. Singh, Bibhuti B. Mishra, Jyotika Sharma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e1117b6c90149c6a59d5744a74a5e5e
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spelling	oai:doaj.org-article:0e1117b6c90149c6a59d5744a74a5e5e2021-12-02T16:04:22ZHelminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis10.1038/s41598-021-92001-92045-2322https://doaj.org/article/0e1117b6c90149c6a59d5744a74a5e5e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92001-9https://doaj.org/toc/2045-2322Abstract 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.Arun ChauhanAtul SharmaJitendra K. TripathiYuyang SunPramod SukumranBrij B. SinghBibhuti B. MishraJyotika SharmaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arun Chauhan Atul Sharma Jitendra K. Tripathi Yuyang Sun Pramod Sukumran Brij B. Singh Bibhuti B. Mishra Jyotika Sharma Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
description	Abstract 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.
format	article
author	Arun Chauhan Atul Sharma Jitendra K. Tripathi Yuyang Sun Pramod Sukumran Brij B. Singh Bibhuti B. Mishra Jyotika Sharma
author_facet	Arun Chauhan Atul Sharma Jitendra K. Tripathi Yuyang Sun Pramod Sukumran Brij B. Singh Bibhuti B. Mishra Jyotika Sharma
author_sort	Arun Chauhan
title	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_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_sort	helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0e1117b6c90149c6a59d5744a74a5e5e
work_keys_str_mv	AT arunchauhan helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis AT atulsharma helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis AT jitendraktripathi helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis AT yuyangsun helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis AT pramodsukumran helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis AT brijbsingh helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis AT bibhutibmishra helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis AT jyotikasharma helminthderivedfactorsinhibitneutrophilextracellulartrapformationandinflammationinbacterialperitonitis
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Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis

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