Abstract

BackgroundThe innate immune system relies upon a wide range of germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors. Different Ig-like immune receptor families have been reported in mammals, birds, amphibians and fish. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways.Methodology/Principal FindingsCarp SITR was found in a substracted cDNA repertoire from carp macrophages, enriched for genes up-regulated in response to the protozoan parasite Trypanoplasma borreli. Carp SITR is a type I protein with two extracellular Ig domains in a unique organisation of a N-proximal V/C2 (or I-) type and a C-proximal V-type Ig domain, devoid of a transmembrane domain or any intracytoplasmic signalling motif. The carp SITR C-proximal V-type Ig domain, in particular, has a close sequence similarity and conserved structural characteristics to the mammalian CD300 molecules. By generating an anti-SITR antibody we could show that SITR protein expression was restricted to cells of the myeloid lineage. Carp SITR is abundantly expressed in macrophages and is secreted upon in vitro stimulation with the protozoan parasite T. borreli. Secretion of SITR protein during in vivo T. borreli infection suggests a role for this IgSF receptor in the host response to this protozoan parasite. Overexpression of carp SITR in mouse macrophages and knock-down of SITR protein expression in carp macrophages, using morpholino antisense technology, provided evidence for the involvement of carp SITR in the parasite-induced NO production.Conclusion/SignificanceWe report the structural and functional characterization of a novel soluble immune-type receptor (SITR) in a teleost fish and propose a role for carp SITR in the NO-mediated response to a protozoan parasite.

Highlights

  • The innate immune system is an ancient form of host defense that relies upon a wide range of non-rearranging, germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors [1,2]

  • leukocyte receptor cluster (LRC) genes can be grouped into different multigene families, which induce leukocyte-Ig-like receptors (LILRs), Ig-like transcripts (ILTs) [8], killer inhibitory receptors (KIRs) [9], platelet collagen receptor glycoprotein VI (GPVI) [10], receptor for IgAFc (FCAR) [11], natural cytotoxicity receptor (NCR) NKp46 [12] and leukocyteassociated inhibitory receptors (LAIRs) [13]

  • A substracted cDNA repertoire from common carp macrophages, enriched for genes up-regulated in response to the protozoan parasite T. borreli, was generated by SSH

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Summary

Introduction

The innate immune system is an ancient form of host defense that relies upon a wide range of non-rearranging, germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors [1,2]. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Iglike domains, a transmembrane segment and a cytoplasmic region that may contain tyrosine residues [2]. Their regulation of effector function is mediated intracellularly by distinct stimulatory or inhibitory pathways. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways

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