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Nucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis.

TitleNucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis.
Publication TypeJournal Article
Year of Publication2007
AuthorsGandotra S, Jang S, Murray PJ, Salgame P, Ehrt S
JournalInfect Immun
Volume75
Issue11
Pagination5127-34
Date Published2007 Nov
ISSN0019-9567
KeywordsAnimals, Colony Count, Microbial, Cytokines, Dendritic Cells, Interleukin-12 Subunit p40, Liver, Lung, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis, Nitric Oxide, Nod2 Signaling Adaptor Protein, Peptidoglycan, Spleen, Toll-Like Receptor 2, Tuberculosis, Tumor Necrosis Factor-alpha, Virulence
Abstract

Nucleotide-binding oligomerization domain proteins (NODs) are modular cytoplasmic proteins implicated in the recognition of peptidoglycan-derived molecules. NOD2 has recently been shown to be important for host cell cytokine responses to Mycobacterium tuberculosis, to synergize with Toll-like receptor 2 (TLR2) in mediating these responses, and thus to serve as a nonredundant recognition receptor for M. tuberculosis. Here, we demonstrate that macrophages and dendritic cells from NOD2-deficient mice were impaired in the production of proinflammatory cytokines and nitric oxide following infection with live, virulent M. tuberculosis. Mycolylarabinogalactan peptidoglycan (PGN), the cell wall core of M. tuberculosis, stimulated macrophages to release tumor necrosis factor (TNF) and interleukin-12p40 in a partially NOD2-dependent manner, and M. tuberculosis PGN required NOD2 for the optimal induction of TNF. However, NOD2-deficient mice were no more susceptible to infection with virulent M. tuberculosis than wild-type mice: they controlled the replication of M. tuberculosis in lung, spleen, and liver as well as wild-type mice, and both genotypes displayed similar lung pathologies. In addition, mice doubly deficient for NOD2 and TLR2 were similarly able to control an M. tuberculosis infection. Thus, NOD2 appears to participate in the recognition of M. tuberculosis by antigen-presenting cells in vitro yet is dispensable for the control of the pathogen during in vivo infection.

DOI10.1128/IAI.00458-07
Alternate JournalInfect Immun
PubMed ID17709422
PubMed Central IDPMC2168277
Grant ListHHSN266200400091C / AI / NIAID NIH HHS / United States
AI055377 / AI / NIAID NIH HHS / United States
R01 HL068525 / HL / NHLBI NIH HHS / United States
R01 AI055377 / AI / NIAID NIH HHS / United States
HHSN266200400091C / / PHS HHS / United States
HL68525 / HL / NHLBI NIH HHS / United States

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