Abstract
This study examined mechanisms contributing to pulmonary immunopathology following acute Mycobacterium tuberculosis (MTB) infection in vivo in a murine model. A/J and C57BL/6 mice were intravenously infected with MTB (Erdman). Pathological differences were found between strains, unrelated to pulmonary load of bacilli. A/J mice developed progressive interstitial pneumonitis, while C57BL/6 mice maintained granuloma formation. The contribution of FAS and FAS ligand-mediated apoptosis was assessed via bioluminescent reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical staining, and TUNEL assessment of DNA fragmentation. Cytokine messages for pulmonary tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as for the lytic molecules perforin and granzyme B, were quantified. Immunohistochemical staining for CD3 receptor was performed to monitor lymphocytic lung infiltration. Soon after infection, A/J mice exhibited increased pulmonary IFN-γ message, concurrent with the appearance of CD3+ lymphocytes distributed throughout the lung. C57BL/6 mice exhibited perivascular cuffing, with no accompanying increase in IFN-γ message. A/J mice also had elevated levels of FAS and FAS ligand message and protein early after infection, while the C57BL/6 mice had no increased expression of these molecules. Both strains exhibited qualitatively similar numbers of TUNEL-positive cells throughout infection, with a marked increase on day 7. Apoptotic cells appeared to co-localize with acid fast bacilli. It is therefore proposed that apoptosis during initial granuloma formation following MTB infection may occur through a FAS/FAS ligand-independent pathway. Moreover, a failure of completion of the FAS/FAS ligand-mediated apoptosis pathway in the A/J mice may contribute to inefficient elimination of lymphocytes, thus further aggravating pulmonary pathology.
Original language | English (US) |
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Pages (from-to) | 211-220 |
Number of pages | 10 |
Journal | Journal of Pathology |
Volume | 190 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2000 |
Externally published | Yes |
Keywords
- Apoptosis
- Bioluminescent RT-PCR
- Cytokines
- FAS
- FAS ligand
- Granzyme B
- Mycobacteria
- Perforin
- Tuberculosis
ASJC Scopus subject areas
- Pathology and Forensic Medicine