Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i>
<i>Mycobacterium mucogenicum</i> (<i>Mmuc</i>), a rapidly growing nontuberculous mycobacterium (NTM), can infect humans (posttraumatic wound infections and catheter-related sepsis). Similar to other NTM species, <i>Mmuc</i> exhibits colony morphologies of rough (&...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2488 |
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| author | Minji Kang Ho Won Kim A-Reum Yu Jeong Seong Yang Seung Heon Lee Ji Won Lee Hoe Sun Yoon Byung Soo Lee Hwan-Woo Park Sung Ki Lee Seungwan Lee Jake Whang Jong-Seok Kim |
| author_facet | Minji Kang Ho Won Kim A-Reum Yu Jeong Seong Yang Seung Heon Lee Ji Won Lee Hoe Sun Yoon Byung Soo Lee Hwan-Woo Park Sung Ki Lee Seungwan Lee Jake Whang Jong-Seok Kim |
| author_sort | Minji Kang |
| collection | DOAJ |
| description | <i>Mycobacterium mucogenicum</i> (<i>Mmuc</i>), a rapidly growing nontuberculous mycobacterium (NTM), can infect humans (posttraumatic wound infections and catheter-related sepsis). Similar to other NTM species, <i>Mmuc</i> exhibits colony morphologies of rough (<i>Mmuc</i>-R) and smooth (<i>Mmuc</i>-S) types. Although there are several case reports on <i>Mmuc</i> infection, no experimental evidence supports that the R-type is more virulent. In addition, the immune response and metabolic reprogramming of <i>Mmuc</i> have not been studied on the basis of morphological characteristics. Thus, a standard ATCC <i>Mmuc</i> strain and two clinical strains were analyzed, and macrophages were generated from mouse bone marrow. Cytokines and cell death were measured by ELISA and FACS, respectively. Mitochondrial respiration and glycolytic changes were measured by XF seahorse. Higher numbers of intracellular bacteria were found in <i>Mmuc</i>-R-infected macrophages than in <i>Mmuc</i>-S-infected macrophages. Additionally, <i>Mmuc</i>-R induced higher levels of the cytokines TNF-α, IL-6, IL-12p40, and IL-10 and induced more BMDM necrotic death. Furthermore, our metabolic data showed marked glycolytic and respiratory differences between the control and each type of <i>Mmuc</i> infection, and changes in these parameters significantly promoted glucose metabolism, extracellular acidification, and oxygen consumption in BMDMs. In conclusion, at least in the strains we tested, <i>Mmuc</i>-R is more virulent, induces a stronger immune response, and shifts bioenergetic metabolism more extensively than the S-type. This study is the first to report differential immune responses and metabolic reprogramming after <i>Mmuc</i> infection and might provide a fundamental basis for additional studies on <i>Mmuc</i> pathogenesis. |
| first_indexed | 2024-03-09T20:38:49Z |
| format | Article |
| id | doaj.art-5909454066234f89839628097b2ba94b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:38:49Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5909454066234f89839628097b2ba94b2023-11-23T23:04:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235248810.3390/ijms23052488Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i>Minji Kang0Ho Won Kim1A-Reum Yu2Jeong Seong Yang3Seung Heon Lee4Ji Won Lee5Hoe Sun Yoon6Byung Soo Lee7Hwan-Woo Park8Sung Ki Lee9Seungwan Lee10Jake Whang11Jong-Seok Kim12Department of Medical Science, Chungnam National University, Daejeon 35365, KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, KoreaKorea Mycobacterium Resource Center (KMRC), Department of Research and Development, The Korean Institute of Tuberculosis, Osong 28158, KoreaKorea Mycobacterium Resource Center (KMRC), Department of Research and Development, The Korean Institute of Tuberculosis, Osong 28158, KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, KoreaDepartment of Ophthalmology, Konyang University Hospital and College of Medicine, Daejeon 35365, KoreaDepartment of Cell Biology, Konyang University College of Medicine, Daejeon 35365, KoreaDepartment of Obstetrics and Gynecology, Konyang University Hospital, Daejeon 35365, KoreaDepartment of Medical Science, Konyang University, 158 Gwanjeodong-ro, Daejeon 35365, KoreaKorea Mycobacterium Resource Center (KMRC), Department of Research and Development, The Korean Institute of Tuberculosis, Osong 28158, KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea<i>Mycobacterium mucogenicum</i> (<i>Mmuc</i>), a rapidly growing nontuberculous mycobacterium (NTM), can infect humans (posttraumatic wound infections and catheter-related sepsis). Similar to other NTM species, <i>Mmuc</i> exhibits colony morphologies of rough (<i>Mmuc</i>-R) and smooth (<i>Mmuc</i>-S) types. Although there are several case reports on <i>Mmuc</i> infection, no experimental evidence supports that the R-type is more virulent. In addition, the immune response and metabolic reprogramming of <i>Mmuc</i> have not been studied on the basis of morphological characteristics. Thus, a standard ATCC <i>Mmuc</i> strain and two clinical strains were analyzed, and macrophages were generated from mouse bone marrow. Cytokines and cell death were measured by ELISA and FACS, respectively. Mitochondrial respiration and glycolytic changes were measured by XF seahorse. Higher numbers of intracellular bacteria were found in <i>Mmuc</i>-R-infected macrophages than in <i>Mmuc</i>-S-infected macrophages. Additionally, <i>Mmuc</i>-R induced higher levels of the cytokines TNF-α, IL-6, IL-12p40, and IL-10 and induced more BMDM necrotic death. Furthermore, our metabolic data showed marked glycolytic and respiratory differences between the control and each type of <i>Mmuc</i> infection, and changes in these parameters significantly promoted glucose metabolism, extracellular acidification, and oxygen consumption in BMDMs. In conclusion, at least in the strains we tested, <i>Mmuc</i>-R is more virulent, induces a stronger immune response, and shifts bioenergetic metabolism more extensively than the S-type. This study is the first to report differential immune responses and metabolic reprogramming after <i>Mmuc</i> infection and might provide a fundamental basis for additional studies on <i>Mmuc</i> pathogenesis.https://www.mdpi.com/1422-0067/23/5/2488<i>Mycobacterium mucogenicum</i>immune responsemetabolismTLR2glycolysismitochondrial respiration |
| spellingShingle | Minji Kang Ho Won Kim A-Reum Yu Jeong Seong Yang Seung Heon Lee Ji Won Lee Hoe Sun Yoon Byung Soo Lee Hwan-Woo Park Sung Ki Lee Seungwan Lee Jake Whang Jong-Seok Kim Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i> International Journal of Molecular Sciences <i>Mycobacterium mucogenicum</i> immune response metabolism TLR2 glycolysis mitochondrial respiration |
| title | Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i> |
| title_full | Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i> |
| title_fullStr | Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i> |
| title_full_unstemmed | Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i> |
| title_short | Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of <i>Mycobacterium mucogenicum</i> |
| title_sort | comparison of macrophage immune responses and metabolic reprogramming in smooth and rough variant infections of i mycobacterium mucogenicum i |
| topic | <i>Mycobacterium mucogenicum</i> immune response metabolism TLR2 glycolysis mitochondrial respiration |
| url | https://www.mdpi.com/1422-0067/23/5/2488 |
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