Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains
Background. Bedaquiline (Bdq) exerts bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, including multidrug-resistant M. tuberculosis strains (MDR-MTBs). However, few reported investigations exist regarding Bdq effects on MDR-MTBs-infected macrophage...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Canadian Journal of Infectious Diseases and Medical Microbiology |
| Online Access: | http://dx.doi.org/10.1155/2022/2703635 |
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| author | Xia-Li Lyu Ting-Ting Lin Jing-Tao Gao Hong-Yan Jia Chuan-Zhi Zhu Zi-Hui Li Jing Dong Qi Sun Wei Shu Sai-Sai Wang Li-Ping Pan Hai-Rong Huang Zong-De Zhang Qi Li |
| author_facet | Xia-Li Lyu Ting-Ting Lin Jing-Tao Gao Hong-Yan Jia Chuan-Zhi Zhu Zi-Hui Li Jing Dong Qi Sun Wei Shu Sai-Sai Wang Li-Ping Pan Hai-Rong Huang Zong-De Zhang Qi Li |
| author_sort | Xia-Li Lyu |
| collection | DOAJ |
| description | Background. Bedaquiline (Bdq) exerts bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, including multidrug-resistant M. tuberculosis strains (MDR-MTBs). However, few reported investigations exist regarding Bdq effects on MDR-MTBs-infected macrophages activities and cytokine secretion. Here, Bdq bactericidal activities against MDR-MTBs and related cellular immune mechanisms were explored. Methods. Macrophages infected with MDR-MTBs or H37Rv received Bdq treatments (4 h/8 h/24 h/48 h) at 1 × the minimum inhibitory concentration (1 × MIC), 10 × MIC and 20 × MIC. Intracellular colony-forming units (CFUs) and culture supernatant IL-12/23 p40, TNF-α, IL-6, and IL-10 were determined using the Luminex® 200TM system. Normally distributed continuous data (mean ± standard deviation) were analyzed using t-test or F-test (SPSS 25.0, P<0.05 deemed statistically significant). Results. (1) 100% of Bdq-treated macrophages (all doses applied over 4–48 h) survived with 0% inhibition of proliferation observed. (2) Intracellular CFUs of Bdq-treated MDR-MTBs-infected macrophages decreased over 4–48 h of treatment, were lower than preadministration and control CFUs, decreased with increasing Bdq dose, and resembled H37Rv-infected group CFUs (48 h). (3) For MDR-MTBs-infected macrophages (various Bdq doses), IL-12/23 p40 levels resembled preadministration group levels and exceeded controls (4 h); TNF-α levels exceeded preadministration group levels (24 h/48 h) and controls (24 h); IL-12/23 p40 and TNF-α levels resembled H37Rv-infected group levels (4 h/8 h/24 h/48 h); IL-6 levels exceeded preadministration and H37Rv-infected group levels (24 h/48 h) and controls (24 h); IL-10 levels resembled preadministration and H37Rv-infected group levels (4 h/8 h/24 h/48 h) and were lower than controls (24 h/48 h); IL-12/23 p40 and IL-10 levels remained unchanged as intracellular CFUs changed, with IL-12/23 p40 levels exceeding controls (4 h) and IL-10 levels remaining lower than controls (24 h/48 h); TNF-α and IL-6 levels increased as intracellular CFUs decreased (24 h/48 h) and exceed controls (24 h). Conclusion. Bdq was strongly bactericidal against intracellular MDR-MTBs and H37Rv in a time-dependent, concentration-dependent manner. Bdq potentially exerted immunomodulatory effects by inducing high-level Th1 cytokine expression (IL-12/23 p40, TNF-α) and low-level Th2 cytokine expression (IL-10). |
| format | Article |
| id | doaj-art-d658324ad60a4ac6bf5951e97f77aa78 |
| institution | Kabale University |
| issn | 1918-1493 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Infectious Diseases and Medical Microbiology |
| spelling | doaj-art-d658324ad60a4ac6bf5951e97f77aa782025-02-03T01:23:14ZengWileyCanadian Journal of Infectious Diseases and Medical Microbiology1918-14932022-01-01202210.1155/2022/2703635Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis StrainsXia-Li Lyu0Ting-Ting Lin1Jing-Tao Gao2Hong-Yan Jia3Chuan-Zhi Zhu4Zi-Hui Li5Jing Dong6Qi Sun7Wei Shu8Sai-Sai Wang9Li-Ping Pan10Hai-Rong Huang11Zong-De Zhang12Qi Li13Beijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBeijing Chest HospitalBackground. Bedaquiline (Bdq) exerts bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, including multidrug-resistant M. tuberculosis strains (MDR-MTBs). However, few reported investigations exist regarding Bdq effects on MDR-MTBs-infected macrophages activities and cytokine secretion. Here, Bdq bactericidal activities against MDR-MTBs and related cellular immune mechanisms were explored. Methods. Macrophages infected with MDR-MTBs or H37Rv received Bdq treatments (4 h/8 h/24 h/48 h) at 1 × the minimum inhibitory concentration (1 × MIC), 10 × MIC and 20 × MIC. Intracellular colony-forming units (CFUs) and culture supernatant IL-12/23 p40, TNF-α, IL-6, and IL-10 were determined using the Luminex® 200TM system. Normally distributed continuous data (mean ± standard deviation) were analyzed using t-test or F-test (SPSS 25.0, P<0.05 deemed statistically significant). Results. (1) 100% of Bdq-treated macrophages (all doses applied over 4–48 h) survived with 0% inhibition of proliferation observed. (2) Intracellular CFUs of Bdq-treated MDR-MTBs-infected macrophages decreased over 4–48 h of treatment, were lower than preadministration and control CFUs, decreased with increasing Bdq dose, and resembled H37Rv-infected group CFUs (48 h). (3) For MDR-MTBs-infected macrophages (various Bdq doses), IL-12/23 p40 levels resembled preadministration group levels and exceeded controls (4 h); TNF-α levels exceeded preadministration group levels (24 h/48 h) and controls (24 h); IL-12/23 p40 and TNF-α levels resembled H37Rv-infected group levels (4 h/8 h/24 h/48 h); IL-6 levels exceeded preadministration and H37Rv-infected group levels (24 h/48 h) and controls (24 h); IL-10 levels resembled preadministration and H37Rv-infected group levels (4 h/8 h/24 h/48 h) and were lower than controls (24 h/48 h); IL-12/23 p40 and IL-10 levels remained unchanged as intracellular CFUs changed, with IL-12/23 p40 levels exceeding controls (4 h) and IL-10 levels remaining lower than controls (24 h/48 h); TNF-α and IL-6 levels increased as intracellular CFUs decreased (24 h/48 h) and exceed controls (24 h). Conclusion. Bdq was strongly bactericidal against intracellular MDR-MTBs and H37Rv in a time-dependent, concentration-dependent manner. Bdq potentially exerted immunomodulatory effects by inducing high-level Th1 cytokine expression (IL-12/23 p40, TNF-α) and low-level Th2 cytokine expression (IL-10).http://dx.doi.org/10.1155/2022/2703635 |
| spellingShingle | Xia-Li Lyu Ting-Ting Lin Jing-Tao Gao Hong-Yan Jia Chuan-Zhi Zhu Zi-Hui Li Jing Dong Qi Sun Wei Shu Sai-Sai Wang Li-Ping Pan Hai-Rong Huang Zong-De Zhang Qi Li Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains Canadian Journal of Infectious Diseases and Medical Microbiology |
| title | Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains |
| title_full | Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains |
| title_fullStr | Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains |
| title_full_unstemmed | Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains |
| title_short | Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains |
| title_sort | effects of bedaquiline on antimicrobial activity and cytokine secretion of macrophages infected with multidrug resistant mycobacterium tuberculosis strains |
| url | http://dx.doi.org/10.1155/2022/2703635 |
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