Work

Identification of nitric oxide synthase as a protective locus against tuberculosis

Year: 1997

Type: article

Abstract: Mutagenesis of the host immune system has helped identify response pathways necessary to combat tuberculosis. Several such pathways may function as activators of a common protective gene: inducible nitric oxide synthase (NOS2). Here we provide direct evidence for this gene controlling primary Mycobacterium tuberculosis infection using mice homozygous for a disrupted NOS2 allele. NOS2(-/-) mice proved highly susceptible, resembling wild-type littermates immunosuppressed by high-dose glucocorticoids, and allowed Mycobacterium tuberculosis to replicate faster in the lungs than reported for other gene-deficient hosts. Susceptibility appeared to be independent of the only known naturally inherited antimicrobial locus, NRAMP1. Progression of chronic tuberculosis in wild-type mice was accelerated by specifically inhibiting NOS2 via administration of N6-(1-iminoethyl)-L-lysine. Together these findings identify NOS2 as a critical host gene for tuberculostasis.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.94.10.5243

Authors: John D. MacMicking, Robert J. North, Ron LaCourse, John S. Mudgett, Shrenik K. Shah, Carl F. Nathan

Institutions: Trudeau Institute, Merck & Co., Inc., Rahway, NJ, USA (United States), Cornell University

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases