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

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1277745

DOI=10.3389/fimmu.2023.1277745

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Pulmonary granuloma diseases caused by <italic>Mycobacterium abscessus</italic> (<italic>M. abscessus</italic>) 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.</p></sec><sec><title>Methods</title><p>In this study, <italic>M. abscessus</italic> embedded within agar beads (agar-AB) was used to develop such a model in C57BL/6JNarl mice.</p></sec><sec><title>Results</title><p>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.</p></sec><sec><title>Discussion</title><p>Although the transient fibrosis persisted for only 3 months, and the pulmonary structure resolved when the pathogen was cleard, this pulmonary fibrosis model for <italic>M. abscessus</italic> infection will provide a novel test platform for development of new drugs, regimens, and therapies.</p></sec>