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Infect. Immun. doi:10.1128/IAI.00458-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

NOD2-deficient mice control infection with Mycobacterium tuberculosis

Department of Microbiology and Immunology, Program in Immunology and Microbial Pathogenesis, Weill Medical College of Cornell University, New York, NY 10021, USA; Department of Medicine, Division of Infectious Diseases, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07101, USA; Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA

^* To whom correspondence should be addressed. Email: sae2004{at}med.cornell.edu.

	Abstract

Nucleotide-binding oligomerization domain (NOD) proteins 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 (Mtb), to synergize with TLR2 in mediating these responses and thus, to serve as a non-redundant recognition receptor for Mtb. Here, we demonstrate that macrophages and dendritic cells from NOD2-deficient mice were impaired in production of proinflammatory cytokines and nitric oxide following infection with live, virulent Mtb. Mycolylarabinogalactan peptidoglycan (mAGP), the cell wall core of Mtb, stimulated macrophages to release TNF and IL-12p40 in a partially NOD2-dependent manner and Mtb peptidoglycan(PGN) required NOD2 for optimal induction of TNF. However, NOD2-deficient mice were no more susceptible to infection with virulent Mtb than wild type mice: they controlled replication of Mtb in lung, spleen and liver as well as wild type mice and both genotypes displayed similar lung pathology. In addition, mice double deficient for NOD2 and Toll-like receptor 2 (TLR2) were similarly able to control an Mtb infection. Thus, NOD2 appears to participate in recognition of Mtb by antigen presenting cells in vitro, yet is dispensable for control of the pathogen during an in vivo infection.