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

Shanti Souriant1, Luciana Balboa2, Maeva Dupont1

  • 1Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; International Associated Laboratory (LIA) CNRS "IM-TB/HIV" (1167), Toulouse, France, and Buenos Aires, Argentina.

Cell Reports
|March 28, 2019
PubMed

Insights

Tuberculosis (TB) and HIV-1 co-infection involves Mycobacterium tuberculosis (Mtb) exacerbating HIV-1. Anti-inflammatory macrophages form tunneling nanotubes (TNTs), facilitating HIV-1 transfer and replication, offering a therapeutic target.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Tuberculosis (TB) and HIV-1 co-infection exhibit synergistic pathogenesis, but the underlying mechanisms remain unclear.
  • Mycobacterium tuberculosis (Mtb) is known to exacerbate HIV-1 progression.
  • Anti-inflammatory macrophages (M(IL-10)) are present in TB-associated microenvironments.

Purpose of the Study:

  • To elucidate the mechanisms by which Mtb exacerbates HIV-1 pathogenesis.
  • To investigate the role of M(IL-10) macrophages in HIV-1 replication and transfer during co-infection.
  • To explore tunneling nanotubes (TNTs) as a potential mediator of viral spread.

Main Methods:

  • Utilized in vitro and ex vivo cell culture systems.
  • Analyzed M(IL-10) macrophage populations and markers (soluble CD163, MerTK) in co-infected non-human primates and patients.
  • Investigated the IL-10/STAT3 signaling pathway and the role of TNTs in viral transfer.

Main Results:

  • M(IL-10) macrophages in TB-associated microenvironments produce high levels of HIV-1.
  • M(IL-10) macrophages are expanded in the lungs of co-infected non-human primates, correlating with disease severity.
  • HIV-1/Mtb co-infected patients show increased M(IL-10) macrophage markers.
  • M(IL-10) macrophages form TNTs, facilitating direct cell-to-cell HIV-1 transfer.
  • Inhibition of TNT formation significantly reduces HIV-1 transfer and M(IL-10) macrophage overproduction.

Conclusions:

  • TNTs facilitate HIV-1 transfer and amplification in M(IL-10) macrophages during Mtb/HIV-1 co-infection.
  • The IL-10/STAT3 signaling pathway is crucial for TNT formation.
  • Targeting TNT formation presents a potential therapeutic strategy for TB/AIDS.
Keywords:
AIDSHIV-1IL-10Mycobacterium tuberculosisSTAT3biomarkerco-infectionmacrophagemonocytetuberculosistunneling nanotubesviral spread

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