Format

Send to

Choose Destination
Cell Rep. 2018 May 8;23(6):1794-1805. doi: 10.1016/j.celrep.2018.04.028.

Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

Author information

1
Laboratory of Mucosal Entry of HIV and Mucosal Immunity, 3I Department, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; INSERM, U1016, Institut Cochin, 75014 Paris, France.
2
Electron Microscopy Facility, Cochin Institute, Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; INSERM, U1016, Institut Cochin, 75014 Paris, France.
3
Laboratory of Mucosal Entry of HIV and Mucosal Immunity, 3I Department, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; INSERM, U1016, Institut Cochin, 75014 Paris, France. Electronic address: morgane.bomsel@inserm.fr.

Abstract

During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4+ T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa.

KEYWORDS:

HIV-1; epithelial cells; mucosa; tissue macrophage; virological synapses

PMID:
29742434
DOI:
10.1016/j.celrep.2018.04.028
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center