Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages

  1. Maeva Dupont
  2. Shanti Souriant
  3. Luciana Balboa
  4. Thien-Phong Vu Manh
  5. Karine Pingris
  6. Stella Rousset
  7. Céline Cougoule
  8. Yoann Rombouts
  9. Renaud Poincloux
  10. Myriam Ben Neji
  11. Carolina Allers
  12. Deepak Kaushal
  13. Marcelo J Kuroda
  14. Susana Benet
  15. Javier Martinez-Picado
  16. Nuria Izquierdo-Useros
  17. Maria del Carmen Sasiain
  18. Isabelle Maridonneau-Parini
  19. Olivier Neyrolles
  20. Christel Vérollet  Is a corresponding author
  21. Geanncarlo Lugo-Villarino  Is a corresponding author
  1. Institute de Pharmacologie et de Biologie Structurale (IPBS), France
  2. Academia Nacional de Medicina/Conicet, Argentina
  3. Aix Marseille University, France
  4. Tulane National Primate Research Center, United States
  5. Tulane University School of Medicine, United States
  6. University of California, Davis, United States
  7. IrsiCaixa AIDS Research Institute, Spain
  8. Universitat Autònoma de Barcelona, Spain
  9. AIDS Research Institute IrsiCaixa, Spain
  10. Université de Toulouse, CNRS, France

Abstract

While tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by which Mycobacterium tuberculosis (Mtb) worsens HIV-1 pathogenesis remain scarce. We showed that HIV-1 infection is exacerbated in macrophages exposed to TB-associated microenvironments due to tunneling nanotube (TNT) formation. To identify molecular factors associated with TNT function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of Siglec-1 receptor. Siglec-1 expression depends on Mtb-induced production of type I interferon (IFN-I). In co-infected non-human primates, Siglec-1 is highly expressed by alveolar macrophages, whose abundance correlates with pathology and activation of IFN-I/STAT1 pathway. Siglec-1 localizes mainly on microtubule-containing TNT that are long and carry HIV-1 cargo. Siglec-1 depletion decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer, and abrogates the exacerbation of HIV-1 infection induced by Mtb. Altogether, we uncover a deleterious role for Siglec-1 in TB-HIV-1 co-infection and opens new avenues to understand TNT biology.

Data availability

The raw data for the transcriptome analysis in this manuscript was made available through the public by a deposit to GEO under the accession code GSE139511.

The following data sets were generated

Article and author information

Author details

  1. Maeva Dupont

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Shanti Souriant

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Luciana Balboa

    IMEX, Academia Nacional de Medicina/Conicet, Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
  4. Thien-Phong Vu Manh

    CIML, Aix Marseille University, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Karine Pingris

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Stella Rousset

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Céline Cougoule

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Yoann Rombouts

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Renaud Poincloux

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Myriam Ben Neji

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Carolina Allers

    Microbiology and Immunology, Tulane National Primate Research Center, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Deepak Kaushal

    Tulane National Primate Research Center, Tulane University School of Medicine, Covington, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Marcelo J Kuroda

    Center for Comparative Medicine and California National Primate Research Center, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Susana Benet

    Retrovirology, IrsiCaixa AIDS Research Institute, Badalona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  15. Javier Martinez-Picado

    AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  16. Nuria Izquierdo-Useros

    Retrovirology, AIDS Research Institute IrsiCaixa, Badalona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  17. Maria del Carmen Sasiain

    IMEX, Academia Nacional de Medicina/Conicet, Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
  18. Isabelle Maridonneau-Parini

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  19. Olivier Neyrolles

    Université de Toulouse, CNRS, Toulouse, France
    Competing interests
    The authors declare that no competing interests exist.
  20. Christel Vérollet

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    For correspondence
    verollet@ipbs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1079-9085
  21. Geanncarlo Lugo-Villarino

    Tuberculosis and Infection Biology (TBIB), Institute de Pharmacologie et de Biologie Structurale (IPBS), Toulouse, France
    For correspondence
    geanncarlo.lugo@ipbs.fr
    Competing interests
    The authors declare that no competing interests exist.

Funding

Agence Nationale de la Recherche (ANRS2014-049)

  • Olivier Neyrolles

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Non‑Human Primate (NHP) samplesAll animal procedures were approved by the Institutional Animal Care and Use Committee of Tulane University, New Orleans, LA and were performed at the Tulane TNPRC, and under approval from IACUC (project numbers P3733, P3794, P3373 and P3628). They were performed in strict accordance with NIH guidelines.

Human subjects: Human SubjectsMonocytes from healthy subjects were provided by Etablissement Français du Sang (EFS), Toulouse, France, under contract 21/PLER/TOU/IPBS01/20130042. According to articles L12434 and R124361 of the French Public Health Code, the contract was approved by the French Ministry of Science and Technology (agreement number AC 2009921). Written informed consents were obtained from the donors before sample collection.

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Received: October 7, 2019
  2. Accepted: March 30, 2020
  3. Accepted Manuscript published: March 30, 2020 (version 1)
  4. Version of Record published: April 21, 2020 (version 2)

Copyright

© 2020, Dupont et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Maeva Dupont
  2. Shanti Souriant
  3. Luciana Balboa
  4. Thien-Phong Vu Manh
  5. Karine Pingris
  6. Stella Rousset
  7. Céline Cougoule
  8. Yoann Rombouts
  9. Renaud Poincloux
  10. Myriam Ben Neji
  11. Carolina Allers
  12. Deepak Kaushal
  13. Marcelo J Kuroda
  14. Susana Benet
  15. Javier Martinez-Picado
  16. Nuria Izquierdo-Useros
  17. Maria del Carmen Sasiain
  18. Isabelle Maridonneau-Parini
  19. Olivier Neyrolles
  20. Christel Vérollet
  21. Geanncarlo Lugo-Villarino
(2020)
Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages
eLife 9:e52535.
https://doi.org/10.7554/eLife.52535

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