Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> Infections
<i>Mycobacterium peregrinum</i> (<i>Mpgm</i>) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. <i>Mpgm</i> is considered an opportunistic p...
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MDPI AG
2023-12-01
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| Online Access: | https://www.mdpi.com/2076-0817/12/12/1446 |
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| author | Ji Won Lee Ho Won Kim A-Reum Yu Hoe Sun Yoon Minji Kang Hwan-Woo Park Sung Ki Lee Jake Whang Jong-Seok Kim |
| author_facet | Ji Won Lee Ho Won Kim A-Reum Yu Hoe Sun Yoon Minji Kang Hwan-Woo Park Sung Ki Lee Jake Whang Jong-Seok Kim |
| author_sort | Ji Won Lee |
| collection | DOAJ |
| description | <i>Mycobacterium peregrinum</i> (<i>Mpgm</i>) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. <i>Mpgm</i> is considered an opportunistic pathogen that causes infection in immunocompromised individuals or those with underlying medical conditions. Although there have been clinical reports on <i>Mpgm</i>, reports of the immune response and metabolic reprogramming have not been published. Thus, we studied standard <i>Mpgm</i>-ATCC and two clinical strains (<i>Mpgm</i>-S and <i>Mpgm</i>-R) using macrophages and mouse bone marrow-derived cells. <i>Mpgm</i> has two types of colony morphologies: smooth and rough. We grew all strains on the 7H10 agar medium to visually validate the morphology. Cytokine levels were measured via ELISA and real-time PCR. The changes in mitochondrial function and glycolysis in <i>Mpgm</i>-infected macrophages were measured using an extracellular flux analyzer. <i>Mpgm</i>-S-infected macrophages showed elevated levels of inflammatory cytokines, including interleukin (IL)-6, IL-12p40, and tumor necrosis factor (TNF)-α, compared to <i>Mpgm</i>-ATCC- and <i>Mpgm</i>-R-infected macrophages. Additionally, our findings revealed metabolic changes in <i>Mpgm</i>-ATCC and two clinical strains (<i>Mpgm</i>-S and <i>Mpgm</i>-R) during infection; significant changes were observed in the mitochondrial respiration, extracellular acidification, and the oxygen consumption of BMDMs upon <i>Mpgm</i>-S infection. In summary, within the strains examined, <i>Mpgm</i>-S displayed greater virulence, triggered a heightened immune response, and induced more profound shifts in bioenergetic metabolism than <i>Mpgm</i>-ATCC and <i>Mpgm</i>-R. This study is the first to document distinct immune responses and metabolic reorganization following <i>Mpgm</i> infection. These findings lay a crucial foundation for further investigations into the pathogenesis of <i>Mpgm.</i> |
| first_indexed | 2024-03-08T20:26:51Z |
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| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-08T20:26:51Z |
| publishDate | 2023-12-01 |
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| spelling | doaj.art-498c7955d72a45119daddfefc53f66f12023-12-22T14:31:01ZengMDPI AGPathogens2076-08172023-12-011212144610.3390/pathogens12121446Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> InfectionsJi Won Lee0Ho Won Kim1A-Reum Yu2Hoe Sun Yoon3Minji Kang4Hwan-Woo Park5Sung Ki Lee6Jake Whang7Jong-Seok Kim8Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of KoreaKorea Mycobacterium Resource Center (KMRC), Department of Research and Development, The Korean Institute of Tuberculosis, Osong 28158, Republic of KoreaDepartment of Cell Biology, College of Medicine, Konyang University, Daejeon 35365, Republic of KoreaDepartment of Obstetrics and Gynecology, Konyang University Hospital, Daejeon 35365, Republic of KoreaKorea Mycobacterium Resource Center (KMRC), Department of Research and Development, The Korean Institute of Tuberculosis, Osong 28158, Republic of KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea<i>Mycobacterium peregrinum</i> (<i>Mpgm</i>) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. <i>Mpgm</i> is considered an opportunistic pathogen that causes infection in immunocompromised individuals or those with underlying medical conditions. Although there have been clinical reports on <i>Mpgm</i>, reports of the immune response and metabolic reprogramming have not been published. Thus, we studied standard <i>Mpgm</i>-ATCC and two clinical strains (<i>Mpgm</i>-S and <i>Mpgm</i>-R) using macrophages and mouse bone marrow-derived cells. <i>Mpgm</i> has two types of colony morphologies: smooth and rough. We grew all strains on the 7H10 agar medium to visually validate the morphology. Cytokine levels were measured via ELISA and real-time PCR. The changes in mitochondrial function and glycolysis in <i>Mpgm</i>-infected macrophages were measured using an extracellular flux analyzer. <i>Mpgm</i>-S-infected macrophages showed elevated levels of inflammatory cytokines, including interleukin (IL)-6, IL-12p40, and tumor necrosis factor (TNF)-α, compared to <i>Mpgm</i>-ATCC- and <i>Mpgm</i>-R-infected macrophages. Additionally, our findings revealed metabolic changes in <i>Mpgm</i>-ATCC and two clinical strains (<i>Mpgm</i>-S and <i>Mpgm</i>-R) during infection; significant changes were observed in the mitochondrial respiration, extracellular acidification, and the oxygen consumption of BMDMs upon <i>Mpgm</i>-S infection. In summary, within the strains examined, <i>Mpgm</i>-S displayed greater virulence, triggered a heightened immune response, and induced more profound shifts in bioenergetic metabolism than <i>Mpgm</i>-ATCC and <i>Mpgm</i>-R. This study is the first to document distinct immune responses and metabolic reorganization following <i>Mpgm</i> infection. These findings lay a crucial foundation for further investigations into the pathogenesis of <i>Mpgm.</i>https://www.mdpi.com/2076-0817/12/12/1446<i>Mycobacterium peregrinum</i>immune responseinflammatory cytokinemetabolic reprogramming |
| spellingShingle | Ji Won Lee Ho Won Kim A-Reum Yu Hoe Sun Yoon Minji Kang Hwan-Woo Park Sung Ki Lee Jake Whang Jong-Seok Kim Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> Infections Pathogens <i>Mycobacterium peregrinum</i> immune response inflammatory cytokine metabolic reprogramming |
| title | Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> Infections |
| title_full | Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> Infections |
| title_fullStr | Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> Infections |
| title_full_unstemmed | Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> Infections |
| title_short | Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of <i>Mycobacterium peregrinum</i> Infections |
| title_sort | differential immune responses and underlying mechanisms of metabolic reprogramming in smooth and rough variants of i mycobacterium peregrinum i infections |
| topic | <i>Mycobacterium peregrinum</i> immune response inflammatory cytokine metabolic reprogramming |
| url | https://www.mdpi.com/2076-0817/12/12/1446 |
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