Schistosoma japonicum egg specific protein SjE16.7 recruits neutrophils and induces inflammatory hepatic granuloma initiation

PLoS Negl Trop Dis. 2014 Feb 13;8(2):e2703. doi: 10.1371/journal.pntd.0002703. eCollection 2014 Feb.

Abstract

Neutrophils are known to play a major role in the egg granulomatous lesions caused by Schistosoma japonicum, but the precise mechanism by which eggs recruit or active neutrophil is unknown. Here we report S. japonicum egg specific EF-hand protein-SjE16.7 is a potent neutrophil recruiter and initiates the egg associated inflammatory granuloma in schistosomiasis. We show that the expression of SjE16.7 at level of both mRNA and protein is restricted to the egg stage. It locates in the miracidium and subshell area of the egg and can be secreted by the egg. The antigenic properties of SjE16.7 strongly suggest a role for SjE16.7 as an egg-derived molecule involved in host-parasite interactions. To study SjE16.7 functions in vivo, we challenged murine air pouch with recombinant SjE16.7. The results showed SjE16.7 trigged more inflammatory cell infiltration than vehicle or control protein. Using peritoneal exudate neutrophils from mice, we found that SjE16.7 significantly induced neutrophil chemotaxis in vitro, and the observed phenotypes were associated with enhanced Rac GTPase activation in SjE16.7 treated cells. Finally, in vivo hepatic granuloma formation model showed SjE16.7 coupled beads recruited more inflammatory cell infiltration than control beads. Our findings suggest SjE16.7 is an important pathogenic factor derived from egg. By recruiting neutrophils and inducing local inflammation, SjE16.7 facilitates eggs to be excreted through gut tissues and also initiates pathology in the liver; therefore SjE16.7 is a possible target for the prevention and treatment of schistosomiasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / chemistry
  • Antigens, Helminth / genetics
  • Antigens, Helminth / metabolism
  • Antigens, Helminth / pharmacology*
  • Cloning, Molecular
  • Female
  • Granuloma / chemically induced*
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Helminth Proteins / pharmacology*
  • Host-Parasite Interactions / drug effects
  • Host-Parasite Interactions / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Schistosoma japonicum* / chemistry
  • Schistosoma japonicum* / genetics
  • Signal Transduction / drug effects

Substances

  • Antigens, Helminth
  • Helminth Proteins
  • Recombinant Proteins

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (NSF-81172808, NSF-30600517) and Foundation for the Author of National Excellent Doctoral Dissertation of PR China (FANEDD-201179). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript.