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Tuberculosis boosts HIV-1 production by macrophages through IL-10/STAT3 dependent tunneling nanotube formation
The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb) and HIV-1 are known to act synergistically, however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture system, we show that human M(IL-10) anti-inflammatory macrophag...
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Published in: | The Journal of immunology (1950) 2019-05, Vol.202 (1_Supplement), p.190-190.79 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb) and HIV-1 are known to act synergistically, however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture system, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironments, produced high levels of HIV-1. In vivo, M(IL-10) macrophages were expanded in lungs of co-infected non-human primates, their number correlated with disease severity, and markers for these cells (soluble CD163 and MerTK) accumulated in the blood of co-infected patients. These M(IL-10) macrophages formed direct cell-to-cell bridges, which we identified as tunneling nanotubes (TNTs) involved in viral transfer. TNT formation required the IL-10/STAT3 signaling pathway, and targeted inhibition of TNTs substantially reduced the enhanced HIV-1 cell-to-cell transfer and overproduction in M(IL-10) macrophages. Our study reveals that TNTs facilitate viral transfer and amplification, promoting TNT formation as a mechanism to be explored in TB/AIDS potential therapeutics. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.202.Supp.190.79 |