Inactivation of the complement anaphylatoxin C5a by secreted products of parasitic nematodes

Dominic Rees-Roberts,Lisa M Mullen,Kleoniki Gounaris,Murray E Selkirk

doi:10.1016/j.ijpara.2009.10.006

Dominic Rees-Roberts, Lisa M Mullen + Show 2 more

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https://doi.org/10.1016/j.ijpara.2009.10.006

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Abstract

Given the importance of the complement anaphylatoxins in cellular recruitment during infection, the ability of secreted products from larval stages of Brugia malayi and Trichinella spiralis to influence C5a-mediated chemotaxis of human peripheral blood granulocytes in vitro was examined. Secreted products from B. malayi microfilariae almost completely abolished chemotaxis. This inhibition was blocked by phenylmethylsulphonyl fluoride, indicating the presence of a serine protease, which was subsequently shown to cleave C5a. In contrast, secreted products from T. spiralis infective larvae showed modest inhibition of C5a-mediated granulocyte chemotaxis, and this was blocked by potato carboxypeptidase inhibitor, an inhibitor of several metallocarboxypeptidases. Adult and larval stages of both parasites were demonstrated to secrete carboxypeptidases which cleaved hippuryl-l-lysine and hippuryl-l-arginine, and the T. spiralis enzyme was partially characterised. The data are discussed with reference to inflammation in parasitic nematode infection.

Highlights

The molecular basis for resistance of nematode parasites to host immunity is of interest given their persistence and inability to vary their antigenic profile
In this study we examined the ability of secreted products from larvae of two species of parasitic nematode to influence C5a-mediated chemotaxis of granulocytes in vitro
Pepstatin partially blocked the action of BmSP, but induced significant chemotaxis when presented to granulocytes alone, the only inhibitor tested which displayed this effect (Fig. 1B)

Summary

Introduction

The molecular basis for resistance of nematode parasites to host immunity is of interest given their persistence and inability to vary their antigenic profile. Inflammation does not always match that expected from secretion of potently antigenic material, for example in lymphatic filariasis, in which individuals frequently harbour high burdens of larval parasites in the circulatory system with no outward sign of infection (Maizels et al, 1995). Chemotherapy of heavily infected individuals invariably induces inflammatory responses as a result of trapping and killing of microfilariae, which may occur following immunological clearance of parasites, suggesting that active infection suppresses inflammation (Maizels et al, 1995). Biochemical and molecular studies of parasite anti-inflammatories has been limited (Maizels and Yazdanbakhsh, 2008). Ancylostoma caninum secretes Neutrophil Inhibitory Factor (NIF), which binds the b integrin CD18/CD11b and inhibits neutrophil adhesion to vascular endothelial cells and subsequent activation (Moyle et al, 1994)

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