Characterization of the tuberculous granuloma in murine and human lungs: Cellular composition and relative tissue oxygen tension

Ming C. Tsai, Soumya Chakravarty, Guofeng Zhu, Jiayong Xu, Kathryn E. Tanaka, Cameron Koch, JoAnn Tufariello, JoAnne Flynn, John Chan

Research output: Contribution to journalArticle

257 Citations (Scopus)

Abstract

The granulomatous reaction is the hallmark of the host response to infection with Mycobacterium tuberculosis. Despite its apparent importance to host defence against the tubercle bacillus, the granulomatous response remains to be completely defined. The present study used histological, immunohistochemical and flow-cytometric analyses to characterize pulmonic granulomatous tissues of tuberculous mice and humans. The kinetics of recruitment of neutrophils, macrophages, dendritic cells, and T and B lymphocytes into the lungs of mice infected aerogenically with the virulent Erdman strain of M. tuberculosis was evaluated in detail in both the acute and persistent phase of infection. A hypoxia-sensing compound based on the 2-nitroimidazole structure (EF5), together with immunohistochemical studies targeting endothelial cells were used to examine the relative oxygen tension in tuberculous granulomatous tissues in mice. The results have provided evidence that: (i) the granulomatous tissues are a highly organized structure whose formation is regulated by orderly recruitment of specific immune cells exhibiting distinct spatial relationship with one another; (ii) the granulomatous reaction, at least in the mouse, may represent an exaggerated response to the tubercle bacillus that can play a role in the development of immunopathology; (iii) B lymphoid aggregates are a prominent feature in both murine and human granulomatous tissues, although the immune cells that are most prominently associated with these clusters vary among the two species; (iv) murine tuberculous granulomatous tissues are relatively aerobic, suggesting that mouse models of persistent tuberculosis may not be suitable for the study of any hypoxic response of M. tuberculosis.

Original languageEnglish (US)
Pages (from-to)218-232
Number of pages15
JournalCellular Microbiology
Volume8
Issue number2
DOIs
StatePublished - Feb 2006

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Granuloma
Tissue
Oxygen
Lung
Mycobacterium tuberculosis
Chemical analysis
Bacilli
Bacillus
Lymphocytes
Neutrophil Infiltration
Macrophages
Endothelial cells
Infection
Dendritic Cells
Tuberculosis
B-Lymphocytes
Endothelial Cells
T-Lymphocytes
Kinetics

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

Characterization of the tuberculous granuloma in murine and human lungs : Cellular composition and relative tissue oxygen tension. / Tsai, Ming C.; Chakravarty, Soumya; Zhu, Guofeng; Xu, Jiayong; Tanaka, Kathryn E.; Koch, Cameron; Tufariello, JoAnn; Flynn, JoAnne; Chan, John.

In: Cellular Microbiology, Vol. 8, No. 2, 02.2006, p. 218-232.

Research output: Contribution to journalArticle

Tsai, Ming C. ; Chakravarty, Soumya ; Zhu, Guofeng ; Xu, Jiayong ; Tanaka, Kathryn E. ; Koch, Cameron ; Tufariello, JoAnn ; Flynn, JoAnne ; Chan, John. / Characterization of the tuberculous granuloma in murine and human lungs : Cellular composition and relative tissue oxygen tension. In: Cellular Microbiology. 2006 ; Vol. 8, No. 2. pp. 218-232.
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