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A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection
Published on: October 5, 2015
Adrenal changes in murine pulmonary tuberculosis; a clue to pathogenesis?
R Hernandez-Pando1, H Orozco, J Honour
1Department of Pathology, Instituto Nacional de la nutrition, Mexico DF, Mexico.
FEMS Immunology and Medical Microbiology
|September 1, 1995
Summary
Tuberculosis infection in mice causes early adrenal hyperplasia followed by atrophy, linked to immune responses. Pre-immunization with Mycobacterium vaccae modulates these adrenal changes, suggesting a role for the cytokine-hypothalamo-pituitary-adrenal axis in disease pathogenesis.
Area of Science:
- Immunology
- Endocrinology
- Microbiology
Background:
- Tuberculosis (TB) infection can lead to profound adrenal changes in humans.
- The adrenal gland's response to Mycobacterium tuberculosis infection in mice is not fully understood.
Purpose of the Study:
- To investigate the dynamic changes in the adrenal gland during Mycobacterium tuberculosis infection in mice.
- To explore the role of immune responses, specifically cytokine profiles, in modulating these adrenal alterations.
- To propose a link between adrenal dysfunction and T cell impairment in TB.
Main Methods:
- Intra-tracheal infection of mice with virulent Mycobacterium tuberculosis H37Rv.
- Histological and weight analysis of adrenal glands at different time points post-infection.
- Electron microscopy to study cellular changes (apoptosis).
- Assessment of delayed-type hypersensitivity (DTH) responses and their sensitivity to TNF-alpha.
- Pre-immunization studies using autoclaved Mycobacterium vaccae to prime specific immune responses (Th1 or mixed cytokine).
Main Results:
- M. tuberculosis infection induced early adrenal hyperplasia, followed by significant atrophy (50% reduction in weight) by 3 weeks, affecting the adrenal cortex but not the medulla.
- Apoptosis was observed in the adrenal cortex via electron microscopy.
- The switch from hyperplasia to atrophy correlated with an IgG1 response to mycobacterial components.
- DTH responses showed differential sensitivity to TNF-alpha during hyperplasia versus atrophy phases.
- Pre-immunization with a Th1-inducing M. vaccae strain attenuated adrenal hyperplasia and prevented atrophy.
- Pre-immunization with a mixed cytokine-inducing M. vaccae strain accelerated and exacerbated adrenal atrophy.
Conclusions:
- The pattern of cytokine release significantly modulates adrenal gland changes during M. tuberculosis infection.
- These findings suggest that alterations in the cytokine-hypothalamo-pituitary-adrenal axis may contribute to T cell dysfunction and immunopathology in human tuberculosis.
- The study provides insights into the pathogenesis of TB, particularly concerning immune-mediated tissue damage.
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