Relationship of survival, organism containment, and granuloma formation in acute murine tuberculosis

Jeffrey K. Actor, Margaret Olsen, Chinnaswamy Jagannath, Robert L. Hunter

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The relationship among organism growth, immunopathology, and survival was studied in C57BL/6 and A/J mice acutely infected with Mycobacterium tuberculosis (MTB) (Erdman). Although organisms grew at similar rates in the lungs of both mouse strains, A/J mice died prior to 14 days after infection, whereas C57BL/6 mice survived twice as long. The lungs of A/J mice exhibited necrotizing interstitial inflammation and widely distributed acid-fast bacilli without granuloma formation. In contrast, the lungs of C57BL/6 mice had relatively mild interstitial inflammation, which was replaced by focal granulomas, and acid-fast bacilli were primarily within granulomas. MTB induced similar granulomas for A/J and C57BL/6 mice in spleen and liver. In the lung, the A/J mice produced only transient messages for interferon-γ (IFN-γ), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-10, and inducible nitric oxide synthase (iNOS). The C57BL/6 mice, in contrast, produced a delayed but sustained response in the lung correlating with granuloma onset and characterized by high induction of IL-6, IFN-γ IL-1β, IL-10, and TNF-α. Responses in the liver and spleen were also evaluated. These results demonstrate that histopathology and cytokine response to MTB infection varies among organs in mice. Increased survival during acute infection may, therefore, depend on the ability to contain organisms within granulomas in the lung.

Original languageEnglish (US)
Pages (from-to)1183-1193
Number of pages11
JournalJournal of Interferon and Cytokine Research
Volume19
Issue number10
DOIs
StatePublished - Nov 8 1999

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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