Schistosoma japonicum Egg Specific Protein SjE16.7 Recruits Neutrophils and Induces Inflammatory Hepatic Granuloma Initiation

Chenyun Wu,Zhaojun Wang,Yanyan Han,Yang Yang,Jianhua Wu,Yan Fang,Linping Tan,Min Chu,Xiaokui Guo,Wei Hu,Ying Wang,Yan Feng,Qing Chen

doi:10.1371/journal.pntd.0002703

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.

Highlights

Schistosomiasis is a neglected tropical disease caused by trematode parasites of the genus Schistosoma
Eggs evoke inflammation leading to a granulomatous response that is necessary for its translocation into the intestinal lumen and excretion in the feces
Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide

Summary

Introduction

Schistosomiasis is a neglected tropical disease caused by trematode parasites of the genus Schistosoma. S. japonicum is the major causative agent of schistosomiasis in South East Asia and China, which mainly cause ‘‘intestinal’’ and ‘‘hepatic schistosomiasis’’. Deposited in the host liver or intestinal tissue, schistosome eggs are the major cause of pathology in schistosomiasis. They are viable metabolically active organisms, and highly antigenic. Eggs evoke inflammation leading to a granulomatous response that is necessary for its translocation into the intestinal lumen and excretion in the feces. This process initiates the pathology in host liver and intestine [2]

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