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

Sci Rep. 2021 Jun 16;11(1):12718. doi: 10.1038/s41598-021-92001-9.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Extracellular Traps / metabolism*
  • Female
  • Klebsiella Infections / immunology*
  • Klebsiella Infections / metabolism
  • Klebsiella Infections / therapy*
  • Klebsiella pneumoniae
  • Ligands
  • Male
  • Mesocestoides*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology
  • Peritonitis / immunology*
  • Peritonitis / metabolism
  • Peritonitis / microbiology
  • Peritonitis / therapy*
  • Reactive Oxygen Species / metabolism
  • Sepsis
  • TRPM Cation Channels / metabolism


  • Ligands
  • Reactive Oxygen Species
  • TRPM Cation Channels
  • TRPM2 protein, mouse