Details

Autor(en) / Beteiligte

• 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
• Siddiqui, Arif
• Arif Siddiqui

Titel

Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains

Ist Teil von

• The Canadian journal of infectious diseases & medical microbiology, 2022, Vol.2022, p.2703635-9

Ort / Verlag

Egypt: Hindawi

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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).