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.
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.
Tuberculosis-associated IFN-I induces Siglec-1 on microtubule-containing tunneling nanotubes and favors HIV-1 spread in macrophagesNCBI Gene Expression Omnibus, GSE139511.
- Olivier Neyrolles
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Bavesh D Kana, University of the Witwatersrand, South Africa
© 2020, Dupont et al.
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