Bcl2 negatively regulates Protective Immune Responses During Mycobacterial Infection
| Autor: | Shakuntala Surender Kumar Saraswati, Chaitenya Verma, Upasana Bandyopadhyay, Aayushi Singh, Vandana Anang, Ankush Kumar Rana, Attinder Chadha, Krishnamurthy Natarajan |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
autophagy QH301-705.5 Stimulation Biology Inhibitor of apoptosis General Biochemistry Genetics and Molecular Biology bcl2 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Immune system Downregulation and upregulation Antigen immune system diseases hemic and lymphatic diseases Biology (General) neoplasms m. bovis bcg Effector Autophagy General Medicine immune responses Respiratory burst 030104 developmental biology 030220 oncology & carcinogenesis bacterial burden Immunology biological phenomena cell phenomena and immunity |
| Zdroj: | Biomolecular Concepts, Vol 12, Iss 1, Pp 94-109 (2021) |
| ISSN: | 1868-503X 1868-5021 |
| DOI: | 10.1515/bmc-2021-0010 |
| Popis: | We previously reported that M. tb on its own as well as together with HIV inhibits macrophage apoptosis by upregulating the expression of Bcl2 and Inhibitor of Apoptosis (IAP). In addition, recent reports from our lab showed that stimulation of either macrophages or BMDCs results in the significant upregulation of Bcl2. In this report, we delineate the role of Bcl2 in mediating defense responses from dendritic cells (BMDCs) during mycobacterial infection. Inhibiting Bcl2 led to a significant decrease in intracellular bacterial burden in BMDCs. To further characterize the role of Bcl2 in modulating defense responses, we inhibited Bcl2 in BMDCs as well as human PBMCs to monitor their activation and functional status in response to mycobacterial infection and stimulation with M. tb antigen Rv3416. Inhibiting Bcl2 generated protective responses including increased expression of co-stimulatory molecules, oxidative burst, pro-inflammatory cytokine expression and autophagy. Finally, co-culturing human PBMCs and BMDCs with antigen-primed T cells increased their proliferation, activation and effector function. These results point towards a critical role for Bcl2 in regulating BMDCs defense responses to mycobacterial infection. |
| Databáze: | OpenAIRE |
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