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Characteristic pro-inflammatory cytokines and host defence cathelicidin peptide produced by human monocyte-derived macrophages infected with Neospora caninum

Published online by Cambridge University Press:  24 November 2017

E. Boucher ,
M. Marin ,
R. Holani ,
M. Young-Speirs ,
D.M. Moore  and
E.R. Cobo Open the ORCID record for E.R. Cobo [Opens in a new window]
E. Boucher
Affiliation:
Bachelor of Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada
M. Marin
Affiliation:
National Research Council (CONICET), Balcarce, Argentina
R. Holani
Affiliation:
Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada
M. Young-Speirs
Affiliation:
Bachelor of Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada
D.M. Moore
Affiliation:
National Research Council (CONICET), Balcarce, Argentina
E.R. Cobo*
Affiliation:
Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada
*
Author for correspondence: Eduardo R. Cobo, E-mail: [email protected]
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Abstract

Neospora caninum is a coccidian intracellular protozoan capable of infecting a wide range of mammals, although severe disease is mostly reported in dogs and cattle. Innate defences triggered by monocytes/macrophages are key in the pathogenesis of neosporosis, as these cells are first-line defenders against intracellular infections. The aim of this study was to characterize infection and innate responses in macrophages infected with N. caninum using a well-known cell model to study macrophage functions (human monocyte THP-1 cells). Intracellular invasion of live tachyzoites occurred as fast as 4 h (confirmed with immunofluorescence microscopy using N. caninum-specific antibodies). Macrophages infected by N. caninum had increased expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-8, IFNγ). Interestingly, N. caninum induced expression of host-defence peptides (cathelicidins), a mechanism of defence never reported for N. caninum infection in macrophages. The expression of cytokines and cathelicidins in macrophages invaded by N. caninum was mediated by mitogen-activated protein kinase (MEK 1/2). Secretion of such innate factors from N. caninum-infected macrophages reduced parasite internalization and promoted the secretion of pro-inflammatory cytokines in naïve macrophages. We concluded that rapid invasion of macrophages by N. caninum triggered protective innate defence mechanisms against intracellular pathogens.

Keywords

CathelicidinscytokinesinfectionmacrophagesmonocytesNeospora caninum
Type
Research Article
Information
Parasitology , Volume 145 , Issue 7 , June 2018 , pp. 871 - 884
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Copyright
Copyright © Cambridge University Press 2017 

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