Mycobacterium paratuberculosis is recognized by Toll-like receptors and NOD2.
Publication year
2007Source
Journal of Leukocyte Biology, 82, 4, (2007), pp. 1011-8ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Internal Medicine
Gastroenterology
Journal title
Journal of Leukocyte Biology
Volume
vol. 82
Issue
iss. 4
Page start
p. 1011
Page end
p. 8
Subject
N4i 1: Pathogenesis and modulation of inflammation; N4i 2: Invasive mycoses and compromised host; N4i 3: Poverty-related infectious diseases; NCEBP 13: Infectious diseases and international health; NCMLS 1: Infection and autoimmunity; UMCN 4.1: Microbial pathogenesis and host defense; UMCN 5.1: Genetic defects of metabolismAbstract
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.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122516]
- Faculty of Medical Sciences [90373]
- Open Access publications [97511]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.