Tuberculosis Exacerbates HIV-1 infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2019

Tuberculosis Exacerbates HIV-1 infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages

Bernard Lagane
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Deepak Kaushal
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Marcelo Kuroda
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Résumé

The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb), and HIV-1 act synergistically; however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture systems, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironments, produce high levels of HIV-1. In vivo, M(IL-10) macrophages are expanded in lungs of co-infected non-human primates, which correlates with disease severity. Further, HIV-1/Mtb co-infected patients display an accumulation of M(IL-10) macrophage markers (soluble CD163 and MerTK). These M(IL-10) macrophages form direct cell-to-cell bridges, which we identified as tunneling nanotubes (TNTs) involved in viral transfer. TNT formation requires the IL-10/STAT3 signaling pathway, and targeted inhibition of TNTs substantially reduces the enhancement of HIV-1 cell-to-cell transfer and overproduction in M(IL-10) macrophages. Our study reveals that TNTs facilitate viral transfer and amplification, thereby promoting TNT formation as a mechanism to be explored in TB/AIDS potential therapeutics.
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Dates et versions

hal-03034321 , version 2 (12-11-2019)
hal-03034321 , version 1 (01-12-2020)

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Shanti Souriant, Luciana Balboa, Maeva Dupont, Karine Pingris, Denise Kviatcovsky, et al.. Tuberculosis Exacerbates HIV-1 infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages. Cell Reports, 2019, 26 (13), pp.3586-3599.e7. ⟨10.1016/j.celrep.2019.02.091⟩. ⟨hal-03034321v2⟩
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