A Trypsin-Sensitive Proteoglycan from the Tapeworm Hymenolepis diminuta Inhibits Murine Neutrophil Chemotaxis in vitro by Suppressing p38 MAP Kinase Activation

J Innate Immun. 2019;11(2):136-149. doi: 10.1159/000492303. Epub 2018 Sep 11.

Abstract

It has emerged that neutrophils can play important roles in the host response following infection with helminth parasites. Mice infected with the tapeworm, Hymenolepis diminuta, are protected from some inflammatory conditions, accompanied by reduced neutrophil tissue infiltration. Thus, the ability of a phosphate-buffered saline-soluble extract of the worm (H. diminuta extract [HdE]) was tested for (1) its ability to activate murine neutrophils (Ca2+ mobilization, reactive oxygen species (ROS) and cytokine production); and (2) affect neutrophil chemotaxis in vitro to the penta-peptide, WKYMVm, the chemokine, KC, and leukotriene B4. HdE was not cytotoxic to neutrophils, elicited a Ca2+ response and ROS, but not, cytokine (KC, interleukin-10, tumour necrosis factor-α) generation. HdE is not a chemotactic stimulus for murine neutrophils. However, a heat- and trypsin-sensitive, acid-insensitive proteoglycan (sensitive to sodium metaperiodate) in the HdE significantly reduced neutrophil chemotaxis towards WKYMVm or KC, but not LTB4. The latter suggested that the HdE interfered with p38 mitogen-activated protein kinase signalling, which is important in WKYMVm chemotaxis. Corroborating this, immunoblotting revealed reduced phosphorylated p38, and the downstream signal heat-shock protein-27, in protein extracts from HdE + WkYMVm treated cells compared to those exposed to the penta-peptide only. We speculate that HdE can be used to modify the outcome of neutrophilic disease and that purification of the bioactive proteoglycan(s) from the extract could be used as a template to design immunomodulatory drugs targeting neutrophils.

Keywords: Chemotaxis; Neutrophils; Parasite-host interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • Antigens, Helminth / metabolism*
  • Calcium Signaling
  • Cell Extracts / pharmacology
  • Cells, Cultured
  • Chemotaxis
  • Cytokines / metabolism
  • Down-Regulation
  • Enzyme Activation
  • Host-Parasite Interactions
  • Hymenolepiasis / immunology*
  • Hymenolepis diminuta / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutrophil Activation
  • Neutrophils / immunology*
  • Proteoglycans / immunology
  • Proteoglycans / metabolism*
  • Trypsin / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antigens, Helminth
  • Cell Extracts
  • Cytokines
  • Proteoglycans
  • p38 Mitogen-Activated Protein Kinases
  • Trypsin

Grant support