Academic Journal
Mycobacterium indicus pranii and Mycobacterium bovis BCG lead to differential macrophage activation in Toll‐like receptor‐dependent manner
| العنوان: | Mycobacterium indicus pranii and Mycobacterium bovis BCG lead to differential macrophage activation in Toll‐like receptor‐dependent manner |
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| المؤلفون: | Kumar, Pawan, Tyagi, Rohit, Das, Gobardhan, Bhaskar, Sangeeta |
| المصدر: | Immunology ; volume 143, issue 2, page 258-268 ; ISSN 0019-2805 1365-2567 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2014 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Summary Mycobacterium indicus pranii ( MIP ) is an atypical mycobacterial species possessing strong immunomodulatory properties. It is a potent vaccine candidate against tuberculosis, promotes Th1 immune response and protects mice from tumours. In previous studies, we demonstrated higher protective efficacy of MIP against experimental tuberculosis as compared with bacillus Calmette–Guérin ( BCG ). Since macrophages play an important role in the pathology of mycobacterial diseases and cancer, in the present study, we evaluated the MIP in live and killed form for macrophage activation potential, compared it with BCG and investigated the underlying mechanisms. High levels of tumour necrosis factor‐ α , interleukin‐12p40 ( IL ‐12p40), IL ‐6 and nitric oxide were produced by MIP ‐stimulated macrophages as compared with BCG ‐stimulated macrophages. Prominent up‐regulation of co‐stimulatory molecules CD 40, CD 80 and CD 86 was also observed in response to MIP . Loss of response in MyD88‐deficient macrophages showed that both MIP and BCG activate the macrophages in a MyD88‐dependent manner. MyD88 signalling pathway culminates in nuclear factor‐ κ B/activator protein‐1 (NF‐ κ B/ AP ‐1) activation and higher activation of NF ‐ κ B/ AP ‐1 was observed in response to MIP . With the help of pharmacological inhibitors and Toll‐like receptor ( TLR ) ‐deficient macrophages, we observed the role of TLR 2, TLR 4 and intracellular TLR s in MIP ‐mediated macrophage activation. Stimulation of HEK 293 cells expressing TLR 2 in homodimeric or heterodimeric form showed that MIP has a distinctly higher level of TLR 2 agonist activity compared with BCG . Further experiments suggested that TLR 2 ligands are well exposed in MIP whereas they are obscured in BCG . Our findings establish the higher macrophage activation potential of MIP compared with BCG and delineate the underlying mechanism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/imm.12306 |
| الاتاحة: | http://dx.doi.org/10.1111/imm.12306 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fimm.12306 https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.12306 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.20CDCC27 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/imm.12306 |
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