Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 221, Issue 10, Pages 1636-1646Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz663
Keywords
B-cell follicles; human granulomatous diseases; lung granuloma; Mycobacterium tuberculosis HN878; pulmonary tuberculosis
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Funding
- Washington University in St. Louis
- National Institutes of Health (NIH) [R01 HL105427, R01 AI134236, R01 AI111914, R01 AI123780]
- NIH [T32 HL007317-42]
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Specific spatial organization of granulomas within the lungs is crucial for protective anti-tuberculosis (TB) immune responses. However, only large animal models such as macaques are thought to reproduce the morphological hallmarks of human TB granulomas. In this study, we show that infection of mice with clinical hypervirulent Mycobacterium tuberculosis (Mtb) HN878 induces human-like granulomas composed of bacilli-loaded macrophages surrounded by lymphocytes and organized localization of germinal centers and B-cell follicles. Infection with laboratory-adapted Mtb H37Rv resulted in granulomas that are characterized by unorganized clusters of macrophages scattered between lymphocytes. An in-depth exploration of the functions of B cells within these follicles suggested diverse roles and the activation of signaling pathways associated with antigen presentation and immune cell recruitment. These findings support the use of clinical Mtb HN878 strain for infection in mice as an appropriate model to study immune parameters associated with human TB granulomas.
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