Inflammatory macrophages associate with tissue injury and fibrosis in a mouse model of tuberculosis

Julie Boucau¹, Jennie Ruelas Castillo¹, Threnesan Naidoo^{2

3}, Yuming Liu⁴, Shatavisha Dasgupta⁵, Neha Jain¹, Nicholas E Jacobson^{4

6}, Kievershen Nargan², Beth A Cimini⁵, Kevin W Eliceiri^{4

6

7

8}, Adrie J C Steyn^{2

9

10}, Amy K Barczak^{1

11

12}

Affiliations

¹ The Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA.
² Africa Health Research Institute (AHRI), University of Kwazulu-Natal, Durban, South Africa.
³ Departments of Forensic & Legal Medicine and Laboratory Medicine & Pathology, Walter Sisulu University, Mthatha, Eastern Cape, South Africa.
⁴ Center for Quantitative Cell Imaging, University of Wisconsin-Madison, Madison, WI, USA.
⁵ Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Morgridge Institute for Research, Madison, WI, USA.
⁸ Department of Medical Physics, University of Wisconsin, Madison, WI, USA.
⁹ Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁰ Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹¹ Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Medicine, Harvard Medical School, Boston, MA, USA.

PMID: 40629518
DOI: 10.1093/infdis/jiaf361

Inflammatory macrophages associate with tissue injury and fibrosis in a mouse model of tuberculosis

Julie Boucau et al. J Infect Dis. 2025.

. 2025 Jul 8:jiaf361.

doi: 10.1093/infdis/jiaf361. Online ahead of print.

Authors

Affiliations

¹ The Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA.
² Africa Health Research Institute (AHRI), University of Kwazulu-Natal, Durban, South Africa.
³ Departments of Forensic & Legal Medicine and Laboratory Medicine & Pathology, Walter Sisulu University, Mthatha, Eastern Cape, South Africa.
⁴ Center for Quantitative Cell Imaging, University of Wisconsin-Madison, Madison, WI, USA.
⁵ Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Morgridge Institute for Research, Madison, WI, USA.
⁸ Department of Medical Physics, University of Wisconsin, Madison, WI, USA.
⁹ Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁰ Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹¹ Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Medicine, Harvard Medical School, Boston, MA, USA.

PMID: 40629518
DOI: 10.1093/infdis/jiaf361

Abstract

Post-tuberculosis lung disease (PTLD) causes a significant burden of global disease. While a consensus definition of PTLD is still in development, parenchymal cavitation, bronchiectasis, and fibrosis are recognized pathologic features that underlie many symptoms and complications of PTLD. The molecular mechanisms driving development of each feature are largely unknown. To facilitate the mechanistic study of tuberculosis (TB)-associated pathologic tissue remodeling and fibrosis, we adapted a mouse model of infection. The morphologies of fibrosis observed in mice were similar to those observed in human tissue samples. Using Second Harmonic Generation microscopy, we found that fibrillar collagen deposition did not resolve with anti-TB antibiotics. Inflammatory transcriptional signatures were persistently upregulated during chronic infection and did not fully resolve after weeks of anti-TB therapy. Inflammatory and fibrosis-associated macrophages similarly persisted during treatment. Immunofluorescence microscopy revealed persistent macrophage populations and shifts in abundance and distribution of type 2 alveolar cells at sites of fibrogenesis.

Keywords: fibrogenesis; fibrosis; host-pathogen; macrophage; mycobacteria; tissue injury; tuberculosis.

© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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Inflammatory macrophages associate with tissue injury and fibrosis in a mouse model of tuberculosis

Affiliations

Inflammatory macrophages associate with tissue injury and fibrosis in a mouse model of tuberculosis

Authors

Affiliations

Abstract

LinkOut - more resources

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