Identification of nitric oxide synthase as a protective locus against tuberculosis. Academic Article uri icon

Overview

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.

publication date

  • May 13, 1997

Research

keywords

  • Carrier Proteins
  • Cation Transport Proteins
  • Immunity, Innate
  • Membrane Proteins
  • Mycobacterium tuberculosis
  • Nitric Oxide Synthase
  • Tuberculosis

Identity

PubMed Central ID

  • PMC24663

Scopus Document Identifier

  • 0031010661

Digital Object Identifier (DOI)

  • 10.1073/pnas.94.10.5243

PubMed ID

  • 9144222

Additional Document Info

volume

  • 94

issue

  • 10