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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Bibliographic Details
Published in:Scientific reports 2021-06, Vol.11 (1), p.12718-12718, Article 12718
Main Authors: Chauhan, Arun, Sharma, Atul, Tripathi, Jitendra K., Sun, Yuyang, Sukumran, Pramod, Singh, Brij B., Mishra, Bibhuti B., Sharma, Jyotika
Format: Article
Language:English
Subjects:
631/250
631/80
692/420
692/699
Animals
Calcium permeability
Cell death
Extracellular Traps - metabolism
Female
Humanities and Social Sciences
Inflammatory diseases
Klebsiella Infections - immunology
Klebsiella Infections - metabolism
Klebsiella Infections - therapy
Klebsiella pneumoniae
Leukocytes (neutrophilic)
Ligands
Male
Mesocestoides
Mice
Mice, Inbred C57BL
multidisciplinary
Neutrophils
Neutrophils - immunology
Parasites
Peritonitis
Peritonitis - immunology
Peritonitis - metabolism
Peritonitis - microbiology
Peritonitis - therapy
Reactive Oxygen Species - metabolism
Science
Science (multidisciplinary)
Sepsis
Transient receptor potential proteins
TRPM Cation Channels - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-92001-9