Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017561/ https://www.ncbi.nlm.nih.gov/pubmed/35449601 http://dx.doi.org/10.1155/2022/2703635 |
_version_ | 1784688801305591808 |
---|---|
author | Lyu, Xia-Li Lin, Ting-Ting Gao, Jing-Tao Jia, Hong-Yan Zhu, Chuan-Zhi Li, Zi-Hui Dong, Jing Sun, Qi Shu, Wei Wang, Sai-Sai Pan, Li-Ping Huang, Hai-Rong Zhang, Zong-De Li, Qi |
author_facet | Lyu, Xia-Li Lin, Ting-Ting Gao, Jing-Tao Jia, Hong-Yan Zhu, Chuan-Zhi Li, Zi-Hui Dong, Jing Sun, Qi Shu, Wei Wang, Sai-Sai Pan, Li-Ping Huang, Hai-Rong Zhang, Zong-De Li, Qi |
author_sort | Lyu, Xia-Li |
collection | PubMed |
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® 200(TM) 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 | Online Article Text |
id | pubmed-9017561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-90175612022-04-20 Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains Lyu, Xia-Li Lin, Ting-Ting Gao, Jing-Tao Jia, Hong-Yan Zhu, Chuan-Zhi Li, Zi-Hui Dong, Jing Sun, Qi Shu, Wei Wang, Sai-Sai Pan, Li-Ping Huang, Hai-Rong Zhang, Zong-De Li, Qi Can J Infect Dis Med Microbiol Research Article 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® 200(TM) 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). Hindawi 2022-04-11 /pmc/articles/PMC9017561/ /pubmed/35449601 http://dx.doi.org/10.1155/2022/2703635 Text en Copyright © 2022 Xia-Li Lyu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Lyu, Xia-Li Lin, Ting-Ting Gao, Jing-Tao Jia, Hong-Yan Zhu, Chuan-Zhi Li, Zi-Hui Dong, Jing Sun, Qi Shu, Wei Wang, Sai-Sai Pan, Li-Ping Huang, Hai-Rong Zhang, Zong-De Li, Qi Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017561/ https://www.ncbi.nlm.nih.gov/pubmed/35449601 http://dx.doi.org/10.1155/2022/2703635 |
work_keys_str_mv | AT lyuxiali effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT lintingting effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT gaojingtao effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT jiahongyan effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT zhuchuanzhi effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT lizihui effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT dongjing effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT sunqi effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT shuwei effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT wangsaisai effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT panliping effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT huanghairong effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT zhangzongde effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains AT liqi effectsofbedaquilineonantimicrobialactivityandcytokinesecretionofmacrophagesinfectedwithmultidrugresistantmycobacteriumtuberculosisstrains |