Bioinformatic analysis of eosinophil activity and its implications for model and target species.

C.J Jenvey,D Alenizi,S Sloan,A Holmes,C Cairns,M.J Stear,F Almasi

doi:10.1017/s0031182019001768

Abstract

Eosinophils are important immune cells that have been implicated in resistance to gastrointestinal nematode (GIN) infections in both naturally and experimentally infected sheep. Proteins of particular importance appear to be IgA-Fc alpha receptor (FcαRI), C-C chemokine receptor type 3 (CCR3), proteoglycan 3 (PRG3, major basic protein 2) and EPX (eosinophil peroxidase). We used known human nucleotide sequences to search the ruminant genomes, followed by translation to protein and sequence alignments to visualize differences between sequences and species. Where a sequence was retrieved for cow, but not for sheep and goat, this was used additionally as a reference sequence. In this review, we show that eosinophil function varies among host species. Consequently, investigations into the mechanisms of ruminant immune responses to GIN should be conducted using the natural host. Specifically, we address differences in protein sequence and structure for eosinophil proteins.

Highlights

Host immune responses to gastrointestinal nematodes (GINs) are dominated by a Th2 immune response; involving antibodies and immune cells, such as immunoglobulin A (IgA), IgE, mast cells and eosinophils
Ruminants naturally and experimentally infected with GIN demonstrate an increase in blood and tissue eosinophilia, implying that eosinophils may be an important mediator of host immune responses to GIN
Both phenotypic and bioinformatic evidence suggest that eosinophil activity against GIN may differ between hosts (Urban et al, 1991; Henderson and Stear, 2006)

Summary

Introduction

Host immune responses to gastrointestinal nematodes (GINs) are dominated by a Th2 immune response; involving antibodies and immune cells, such as immunoglobulin A (IgA), IgE, mast cells and eosinophils. Ruminants naturally and experimentally infected with GIN demonstrate an increase in blood and tissue eosinophilia, implying that eosinophils may be an important mediator of host immune responses to GIN. Both phenotypic and bioinformatic evidence suggest that eosinophil activity against GIN may differ between hosts (Urban et al, 1991; Henderson and Stear, 2006). We addressed differences in protein sequence and structure for eosinophil proteins These proteins included IgA and its receptor, FcαRI, interleukin (IL)-5 and its receptor, IL-5Rα, eotaxin and its receptor, CCR3, major basic protein (MBP, PRG3) and eosinophil peroxidase (EPX). We used known human nucleotide sequences to search the ruminant genomes (Bos taurus, cow; Ovis aries, sheep; Capra hircus, goat), retrieved sequences (Supplementary Table 1), followed by translation to protein and sequence alignments to visualize differences between sequences and species

Eosinophils and GIN infections

Theoretical pI

Goat EPX lacks a nitrosylated tyrosine

Findings

Directions for future research