title: Nucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis.
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.
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, Box 62, 1300 York Avenue, New York, NY 10021, USA.
authors: Sheetal
authors: S
authors: Gandotra
authors: Sihyug
authors: S
authors: Jang
authors: Peter J
authors: PJ
authors: Murray
authors: Padmini
authors: P
authors: Salgame
authors: Sabine
authors: S
authors: Ehrt
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D009569:Nitric Oxide / Q000096:biosynthesis; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency* / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D013154:Spleen / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000172:deficiency; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014774:Virulence
chemical_list: D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D010457:Peptidoglycan; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide
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