Mycobacterium paratuberculosis is recognized by Toll-like receptors and NOD2

Autor: Reinout van Crevel, Jos W. M. van der Meer, Bart Jan Kullberg, Dennis M. L. Langenberg, Tom H. M. Ottenhoff, Gerben Ferwerda, Mihai G. Netea, Stephen E. Girardin, Dirk J. de Jong
Rok vydání: 2007
Předmět:
Infectious diseases and international health [NCEBP 13]
medicine.medical_treatment
Immunology
Nod2 Signaling Adaptor Protein
Paratuberculosis
Stimulation
CHO Cells
Biology
Invasive mycoses and compromised host [N4i 2]
Mice
Cricetulus
Crohn Disease
Cricetinae
medicine
Animals
Humans
Immunology and Allergy
Mice
Knockout
Innate immune system
Macrophages
Poverty-related infectious diseases [N4i 3]
Cell Biology
medicine.disease
Molecular biology
Immunity
Innate
Toll-Like Receptor 2
Mycobacterium avium subsp. paratuberculosis
Toll-Like Receptor 4
Pathogenesis and modulation of inflammation [N4i 1]
Adaptor Proteins
Vesicular Transport
TLR2
Cytokine
Genetic defects of metabolism [UMCN 5.1]
TRIF
Mutation
Myeloid Differentiation Factor 88
TLR4
Cytokines
Tumor necrosis factor alpha
Microbial pathogenesis and host defense [UMCN 4.1]
Infection and autoimmunity [NCMLS 1]
Zdroj: Journal of Leukocyte Biology, 82, 4, pp. 1011-8
Journal of Leukocyte Biology, 82, 1011-8
ISSN: 0741-5400
Popis: Contains fulltext : 53634.pdf (Publisher’s version ) (Open Access) Mycobacterium paratuberculosis has been suggested to be involved in the pathogenesis of Crohn's disease (CD). The importance of microorganisms in CD is supported by the association of CD with mutations in the intracellular pathogen recognition receptor (PRR) nucleotide-binding oligomerization domain 2 (NOD2). The aim of this study is to investigate the PRR involved in the recognition of M. paratuberculosis. Methods used include in vitro stimulation of transfected cell lines, murine macrophages, and human PBMC. M. paratuberculosis stimulated human TLR2 (hTLR2)-Chinese hamster ovary (CHO) cells predominantly and hTLR4-CHO cells modestly. Macrophages from TLR2 and TLR4 knockout mice produced less cytokines compared with controls after stimulation with M. paratuberculosis. TLR4 inhibition in human PBMC reduced cytokine production only after stimulation with live M. paratuberculosis. TLR-induced TNF-alpha, IL-1beta, and IL-10 production is mediated through MyD88, whereas Toll-IL-1R domain-containing adaptor inducing IFN-beta (TRIF) promoted the release of IL-1beta. hNOD2-human embryo kidney (HEK) cells, but not hNOD1-HEK cells, responded to stimulation with M. paratuberculosis. PBMC of individuals homozygous for the 3020insC NOD2 mutation showed a 70% defective cytokine response after stimulation with M. paratuberculosis. These results demonstrate that TLR2, TLR4, and NOD2 are involved in the recognition of M. paratuberculosis by the innate immune system.
Databáze: OpenAIRE
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