Mycobacterium tuberculosis and Human Immunodeficiency Virus Type 1 Cooperatively Modulate Macrophage Apoptosis via Toll Like Receptor 2 and Calcium Homeostasis
| Autor: | Nabab Khan, Cecil Antony, Subhash Mehto, Brijendra K Tiwari, Shahid Jameel, Krishnamurthy Natarajan, Mohit Vashishta, Yogendra Singh, Rahul Arya, Arti Selvakumar |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
chemistry.chemical_element
lcsh:Medicine Apoptosis HIV Infections Biology Calcium Calcium in biology Mycobacterium tuberculosis Bacterial Proteins Homeostasis Humans Tuberculosis nef Gene Products Human Immunodeficiency Virus Antigens RNA Small Interfering lcsh:Science Cells Cultured Respiratory Burst Membrane Potential Mitochondrial Calcium metabolism Toll-like receptor Multidisciplinary Coinfection Macrophages lcsh:R Cytochromes c biology.organism_classification Toll-Like Receptor 2 Cell biology HEK293 Cells Gene Expression Regulation chemistry Second messenger system HIV-1 Leukocytes Mononuclear lcsh:Q Signal transduction Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 7, p e0131767 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The emergence of drug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) together with reports of co-infections with the human immunodeficiency virus (HIV) has renewed interest to better understand the intricate mechanisms prevalent during co-infections. In this study we report a synergistic effect of M. tuberculosis and HIV-1, and their antigens Rv3416 and Nef, respectively, in inhibiting apoptosis of macrophages. This inhibition involves the TLR2 pathway and second messengers that play complementing and contrasting roles in regulating apoptosis. Interestingly, the route of calcium influx into cells differentially regulates apoptosis during antigenic co-stimulation. While calcium released from intracellular stores was anti-apoptotic, calcium influx from the external milieu was pro-apoptotic. Further, molecular sensors of intracellular calcium release aid in antigen mediated inhibition of apoptosis. A cross-regulation between oxidative burst and differential routing of calcium influx governed apoptosis. Interestingly, the HIV-1 Nef supported anti-apoptotic responses in macrophages whereas Vpu had no significant effect. These results point to a synergistic liaison between M. tuberculosis and HIV-1 in regulating macrophage apoptosis. |
| Databáze: | OpenAIRE |
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