Pathological granuloma fibrosis induced by agar-embedded Mycobacterium abscessus in C57BL/6JNarl mice

Shiu-Ju Yang; Chih-Hao Hsu; Chi-Yun Lai; Pei-Chu Tsai; Yung-Deng Song; Chang-Ching Yeh; Yih-Yuan Chen; Horng-Yunn Dou

doi:10.3389/fimmu.2023.1277745

Pathological granuloma fibrosis induced by agar-embedded Mycobacterium abscessus in C57BL/6JNarl mice

Front Immunol. 2023 Dec 11:14:1277745. doi: 10.3389/fimmu.2023.1277745. eCollection 2023.

Authors

Shiu-Ju Yang¹, Chih-Hao Hsu¹, Chi-Yun Lai², Pei-Chu Tsai¹, Yung-Deng Song¹, Chang-Ching Yeh¹, Yih-Yuan Chen³, Horng-Yunn Dou¹

Affiliations

¹ National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
² Pathology Core Laboratory, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
³ Department of Biochemical Science and Technology, National Chiayi University, Chia-Yi, Taiwan.

Abstract

Introduction: Pulmonary granuloma diseases caused by Mycobacterium abscessus (M. abscessus) have increased in past decades, and drug-resistance in this pathogen is a growing public health concern. Therefore, an animal model of chronic granuloma disease is urgently needed.

Methods: In this study, M. abscessus embedded within agar beads (agar-AB) was used to develop such a model in C57BL/6JNarl mice.

Results: Chronic infection was sustained for at least 3 months after agar-AB infection, visible granulomas spread in the lungs, and giant cells and foamy cells appeared in the granulomas. More importantly, pulmonary fibrosis progressed for 3 months, and collagen fibers were detected by Masson trichrome staining. Further, inducible nitric oxide synthase (iNOS) was highly expressed within the alveolar space, and the fibrosis-mediator transforming growth factor beta (TGF-β) began to be expressed at 1 month. Hypoxia-inducible factor (HIF-1α) expression also increased, which aided in normalizing oxygen partial pressure.

Discussion: Although the transient fibrosis persisted for only 3 months, and the pulmonary structure resolved when the pathogen was cleard, this pulmonary fibrosis model for M. abscessus infection will provide a novel test platform for development of new drugs, regimens, and therapies.

Keywords: fibrosis; hypoxia; immunocompetent mice; mycobacterium abscessus; pulmonary granuloma diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agar / metabolism
Animals
Fibrosis
Granuloma / pathology
Mice
Mice, Inbred C57BL
Mycobacterium abscessus* / metabolism
Pulmonary Fibrosis*

Substances

Agar

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project was supported by Intramural grants provided by the National Health Research Institutes, Taiwan (11A1-IVPP04-014 and 11A1-IVSP06-014).