Innate immune receptors in carp: recognition of protozoan parasites

C.M.S. Ribeiro

Research output: Thesisinternal PhD, WU

Abstract

This PhD thesis reports on pattern recognition receptors involved in the immune responses of common carp (Cyprinus carpio) to two protozoan parasites Trypanoplasma borreli and Trypanosoma carassii. The immune responses of carp are fundamentally different when comparing these two extracellular blood parasites. T. borreli induces a characteristically high production of nitric oxide by macrophages, whereas T. carassii parasites seem to preferentially induce an alternative state of macrophage activation. These differences could be driven by differences in the initial engagement of pattern recognition receptors on carp macrophages with either of the two types of parasites. Based on known host-parasite interactions in mammalian vertebrates, Toll-like receptor 2 (TLR2) and TLR9 were selected as candidate receptors for parasite recognition by receptors carp macrophages. Transfection of human cell cultures with carp TLR2 and overexpression of TLR2 in carp macrophages, corroborated the ability of this receptor to bind peptidoglycan from Gram-positive bacteria and glycosylphosphatidylinositol anchors from protozoan parasites. The parasite T. carassii, in particular, induced a TLR2-mediated formation of the cytokine IL-23, leading to a Th17-like immune response in fish infected with T. carassii. Transfection of human cell cultures with carp TLR9 indicated this receptor recognizes bacterial DNA, but not protozoan DNA, and studies in carp macrophages indicated this recognition to be protease-dependent. A novel pattern recognition receptor of carp, named Soluble Immune-Type Receptor (SITR), was identified by investigating an enriched cDNA repertoire from macrophages stimulated by T. borreli. SITR is abundantly expressed in carp macrophages and seems to be secreted upon stimulation with T. borreli. Overexpression of SITR in mouse macrophages and knock-down of SITR in carp macrophages provided evidence for the involvement of this receptor in T. borreli-induced production of nitric oxide. The results presented in this PhD thesis have shed light on the evolution of innate immune receptors involved in the recognition of pathogens.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Savelkoul, Huub, Promotor
  • Wiegertjes, Geert, Co-promotor
Award date1 Oct 2010
Place of Publication[S.l.
Publisher
Print ISBNs9789085857747
Publication statusPublished - 2010

Fingerprint

Carps
Parasites
Macrophages
Toll-Like Receptor 2
Pattern Recognition Receptors
Protozoan DNA
Transfection
Nitric Oxide
Cell Culture Techniques
Toll-Like Receptor 9
Interleukin-23
Trypanosoma
Host-Parasite Interactions
Bacterial DNA
Glycosylphosphatidylinositols
Macrophage Activation
Peptidoglycan
Gram-Positive Bacteria
Vertebrates
Fishes

Keywords

  • carp
  • immune response
  • receptors
  • protozoa
  • parasites
  • immune system
  • vaccines
  • adjuvants
  • immunology
  • immunity

Cite this

Ribeiro, C.M.S.. / Innate immune receptors in carp: recognition of protozoan parasites. [S.l. : S.n., 2010. 217 p.
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title = "Innate immune receptors in carp: recognition of protozoan parasites",
abstract = "This PhD thesis reports on pattern recognition receptors involved in the immune responses of common carp (Cyprinus carpio) to two protozoan parasites Trypanoplasma borreli and Trypanosoma carassii. The immune responses of carp are fundamentally different when comparing these two extracellular blood parasites. T. borreli induces a characteristically high production of nitric oxide by macrophages, whereas T. carassii parasites seem to preferentially induce an alternative state of macrophage activation. These differences could be driven by differences in the initial engagement of pattern recognition receptors on carp macrophages with either of the two types of parasites. Based on known host-parasite interactions in mammalian vertebrates, Toll-like receptor 2 (TLR2) and TLR9 were selected as candidate receptors for parasite recognition by receptors carp macrophages. Transfection of human cell cultures with carp TLR2 and overexpression of TLR2 in carp macrophages, corroborated the ability of this receptor to bind peptidoglycan from Gram-positive bacteria and glycosylphosphatidylinositol anchors from protozoan parasites. The parasite T. carassii, in particular, induced a TLR2-mediated formation of the cytokine IL-23, leading to a Th17-like immune response in fish infected with T. carassii. Transfection of human cell cultures with carp TLR9 indicated this receptor recognizes bacterial DNA, but not protozoan DNA, and studies in carp macrophages indicated this recognition to be protease-dependent. A novel pattern recognition receptor of carp, named Soluble Immune-Type Receptor (SITR), was identified by investigating an enriched cDNA repertoire from macrophages stimulated by T. borreli. SITR is abundantly expressed in carp macrophages and seems to be secreted upon stimulation with T. borreli. Overexpression of SITR in mouse macrophages and knock-down of SITR in carp macrophages provided evidence for the involvement of this receptor in T. borreli-induced production of nitric oxide. The results presented in this PhD thesis have shed light on the evolution of innate immune receptors involved in the recognition of pathogens.",
keywords = "karper, immuniteitsreactie, receptoren, protozoa, parasieten, immuunsysteem, vaccins, hulpstoffen, immunologie, immuniteit, carp, immune response, receptors, protozoa, parasites, immune system, vaccines, adjuvants, immunology, immunity",
author = "C.M.S. Ribeiro",
note = "WU thesis 4885",
year = "2010",
language = "English",
isbn = "9789085857747",
publisher = "S.n.",
school = "Wageningen University",

}

Ribeiro, CMS 2010, 'Innate immune receptors in carp: recognition of protozoan parasites', Doctor of Philosophy, Wageningen University, [S.l..

Innate immune receptors in carp: recognition of protozoan parasites. / Ribeiro, C.M.S.

[S.l. : S.n., 2010. 217 p.

Research output: Thesisinternal PhD, WU

TY - THES

T1 - Innate immune receptors in carp: recognition of protozoan parasites

AU - Ribeiro, C.M.S.

N1 - WU thesis 4885

PY - 2010

Y1 - 2010

N2 - This PhD thesis reports on pattern recognition receptors involved in the immune responses of common carp (Cyprinus carpio) to two protozoan parasites Trypanoplasma borreli and Trypanosoma carassii. The immune responses of carp are fundamentally different when comparing these two extracellular blood parasites. T. borreli induces a characteristically high production of nitric oxide by macrophages, whereas T. carassii parasites seem to preferentially induce an alternative state of macrophage activation. These differences could be driven by differences in the initial engagement of pattern recognition receptors on carp macrophages with either of the two types of parasites. Based on known host-parasite interactions in mammalian vertebrates, Toll-like receptor 2 (TLR2) and TLR9 were selected as candidate receptors for parasite recognition by receptors carp macrophages. Transfection of human cell cultures with carp TLR2 and overexpression of TLR2 in carp macrophages, corroborated the ability of this receptor to bind peptidoglycan from Gram-positive bacteria and glycosylphosphatidylinositol anchors from protozoan parasites. The parasite T. carassii, in particular, induced a TLR2-mediated formation of the cytokine IL-23, leading to a Th17-like immune response in fish infected with T. carassii. Transfection of human cell cultures with carp TLR9 indicated this receptor recognizes bacterial DNA, but not protozoan DNA, and studies in carp macrophages indicated this recognition to be protease-dependent. A novel pattern recognition receptor of carp, named Soluble Immune-Type Receptor (SITR), was identified by investigating an enriched cDNA repertoire from macrophages stimulated by T. borreli. SITR is abundantly expressed in carp macrophages and seems to be secreted upon stimulation with T. borreli. Overexpression of SITR in mouse macrophages and knock-down of SITR in carp macrophages provided evidence for the involvement of this receptor in T. borreli-induced production of nitric oxide. The results presented in this PhD thesis have shed light on the evolution of innate immune receptors involved in the recognition of pathogens.

AB - This PhD thesis reports on pattern recognition receptors involved in the immune responses of common carp (Cyprinus carpio) to two protozoan parasites Trypanoplasma borreli and Trypanosoma carassii. The immune responses of carp are fundamentally different when comparing these two extracellular blood parasites. T. borreli induces a characteristically high production of nitric oxide by macrophages, whereas T. carassii parasites seem to preferentially induce an alternative state of macrophage activation. These differences could be driven by differences in the initial engagement of pattern recognition receptors on carp macrophages with either of the two types of parasites. Based on known host-parasite interactions in mammalian vertebrates, Toll-like receptor 2 (TLR2) and TLR9 were selected as candidate receptors for parasite recognition by receptors carp macrophages. Transfection of human cell cultures with carp TLR2 and overexpression of TLR2 in carp macrophages, corroborated the ability of this receptor to bind peptidoglycan from Gram-positive bacteria and glycosylphosphatidylinositol anchors from protozoan parasites. The parasite T. carassii, in particular, induced a TLR2-mediated formation of the cytokine IL-23, leading to a Th17-like immune response in fish infected with T. carassii. Transfection of human cell cultures with carp TLR9 indicated this receptor recognizes bacterial DNA, but not protozoan DNA, and studies in carp macrophages indicated this recognition to be protease-dependent. A novel pattern recognition receptor of carp, named Soluble Immune-Type Receptor (SITR), was identified by investigating an enriched cDNA repertoire from macrophages stimulated by T. borreli. SITR is abundantly expressed in carp macrophages and seems to be secreted upon stimulation with T. borreli. Overexpression of SITR in mouse macrophages and knock-down of SITR in carp macrophages provided evidence for the involvement of this receptor in T. borreli-induced production of nitric oxide. The results presented in this PhD thesis have shed light on the evolution of innate immune receptors involved in the recognition of pathogens.

KW - karper

KW - immuniteitsreactie

KW - receptoren

KW - protozoa

KW - parasieten

KW - immuunsysteem

KW - vaccins

KW - hulpstoffen

KW - immunologie

KW - immuniteit

KW - carp

KW - immune response

KW - receptors

KW - protozoa

KW - parasites

KW - immune system

KW - vaccines

KW - adjuvants

KW - immunology

KW - immunity

M3 - internal PhD, WU

SN - 9789085857747

PB - S.n.

CY - [S.l.

ER -