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Siglec-1: Bridging the synergy between Mycobacterium tuberculosis and HIV-1

The synergistic relationship between the AIDS virus, HIV-1, and the causative agent of tuberculosis,Mycobacterium tuberculosis, is known to result in increased proliferation of both pathogens and associated pathogenesis, considerably worsening the prognosis for co-infected patients. Increased tuberculosis severity in such patients is largely a consequence of HIV-1-induced T-cell decay, but howM. tuberculosisexacerbates HIV-1-associated pathology in co-infected patients is still poorly understood. One possible link is through macrophages, which are host cells forM. tuberculosisand HIV-1 and play an important role in HIV-1 pathogenesis. In the context of an international collaboration (LIA)IM-TB/HIV, a collaboration between the laboratory of Drs. MDC Sasiain and L Balboa at the IMEX CONICET- Academia Nacional de Medicina of Buenos Aires (Argentina) and two laboratories at IPBS, the receptor Siglec-1 (CD169 or sialoadhesin) was identified as a key tuberculosis-driven factor for the exacerbation of HIV-1 infection in macrophages. These results are published in the journal eLife on March 30th, 2020.


在这部作品中,researche德赢vwin手机版rs showed thatM. tuberculosistriggers the type I interferon (IFN-I)/Signal transducer and activator of transcription 1 (STAT1) pathway to induce high expression of the Siglec-1 receptor. InM. tuberculosis-simian immunodeficiency virus (SIV) co-infected non-human primates, Siglec-1 is highly expressed by alveolar macrophages, whose abundance correlates with pathology and activation of the IFN-I/STAT1 pathway.
Interestingly, the researchers observed that Siglec-1 is present on tunneling nanotubes (TNT), long-range membranous and F-actin-containing tubes, and in particular on the “thick” (>0.7 μm in diameter) subtype that are enriched in microtubules and known to transport organelles (e.g., mitochondria). Siglec-1+ thick TNT exhibited greater length and contained high intracellular cargo of HIV-1 proteins and mitochondria. Strikingly, inhibition of Siglec-1 led to a decrease in thick TNT length, HIV-1 capture and cell-to-cell transfer of HIV-1, and abrogation of the exacerbation of HIV-1 infection induced by tuberculosis-associated microenvironment.
Collectively, this study addresses an area of primary public health importance and reveals that Siglec-1 is a key player in the synergy betweenM. tuberculosisand HIV-1. Indeed, its exclusive localization on thick TNT opens new venues for further delineating how these two pathogens modulate the host immune response, and it provides leads for improvedM. tuberculosis-HIV co-infection diagnostics and therapeutics.

Siglec-1 localizes on HIV-1-containing tunneling nanotubes formed under the influence of a
tuberculosis-associated microenvironment.

Siglec-1 (red), HIV-Gag in (green) and cell membrane (wheat germ agglutinin staining in blue). Scale bar, 10 μm.

This work was funded by the CNRS, the University Toulouse III-Paul Sabatier, the Ministry of Research, Higher Education and Innovation, the National Agency for Research on AIDS and Viral Hepatitis, Sidaction, the National Research Agency, the ECOS-Sud programme and the Foundation for Medical Research.

Reference

Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages
Dupont M., Souriant S., Balboa L., Vu Manh T-P., Pingris K., Rousset S., Cougoule C., Rombouts Y., Poincloux R., Ben Neji M., Allers C., Kaushal D., Kuroda MJ., Benet S., Martinez-Picado J., Izquierdo-Useros N., del Carmen Sasiain M., I Maridonneau-Parini I*, Neyrolles O*, Vérollet C* and Lugo-Villarino G*. eLife. 2020 March 30. 9: e52535. DOI: 10.7554/eLife.52535

Contacts

Researchers IPBS: Christel Vérollet | verollet@ipbs.fr | 05 61 17 54 56 & Geanncarlo Lugo | lugo@ipbs.fr | 05 61 17 59 10
Press IPBS: Francoise Viala | Communication@ipbs.fr | 06 01 26 52 59