Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
Autor: | Arun Chauhan, Brij B. Singh, Pramod Sukumran, Yuyang Sun, Bibhuti B. Mishra, Jitendra Kumar Tripathi, Atul Sharma, Jyotika Sharma |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
Cell biology Programmed cell death Neutrophils Bacterial Peritonitis Science Immunology TRPM Cation Channels Peritonitis Diseases Inflammation Pathogenesis Ligands Extracellular Traps Article Microbiology Sepsis Mice Mesocestoides medicine Animals TRPM2 Multidisciplinary Chemistry Neutrophil extracellular traps medicine.disease Klebsiella Infections Mice Inbred C57BL Klebsiella pneumoniae Medicine Female medicine.symptom Reactive Oxygen Species |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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