Tissue-like environments shape functional interactions of HIV-1 with immature dendritic cells.

Autor: Gallucci L; Department of Infectious Diseases, Integrative Virology, CIID, University Hospital Heidelberg, Heidelberg, Germany., Abele T; Biophysical Engineering Group, Max Planck Institute for Medical Research, Heidelberg, Germany.; ZMBH, Center for Molecular Biology, Heidelberg University, Heidelberg, Germany., Fronza R; ProtaGene CGT GmbH, Heidelberg, Germany., Stolp B; Department of Infectious Diseases, Integrative Virology, CIID, University Hospital Heidelberg, Heidelberg, Germany., Laketa V; Department of Infectious Diseases, Virology, CIID, Heidelberg University Hospital, Heidelberg, Germany.; German Centre for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany., Sid Ahmed S; Department of Infectious Diseases, Integrative Virology, CIID, University Hospital Heidelberg, Heidelberg, Germany., Flemming A; Department of Infectious Diseases, Virology, CIID, Heidelberg University Hospital, Heidelberg, Germany., Müller B; Department of Infectious Diseases, Virology, CIID, Heidelberg University Hospital, Heidelberg, Germany., Göpfrich K; Biophysical Engineering Group, Max Planck Institute for Medical Research, Heidelberg, Germany.; ZMBH, Center for Molecular Biology, Heidelberg University, Heidelberg, Germany., Fackler OT; Department of Infectious Diseases, Integrative Virology, CIID, University Hospital Heidelberg, Heidelberg, Germany.; German Centre for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2023 Jun 05; Vol. 24 (6), pp. e56818. Date of Electronic Publication: 2023 Apr 12.
DOI: 10.15252/embr.202356818
Abstrakt: Immature dendritic cells (iDCs) migrate in microenvironments with distinct cell and extracellular matrix densities in vivo and contribute to HIV-1 dissemination and mounting of antiviral immune responses. Here, we find that, compared to standard 2D suspension cultures, 3D collagen as tissue-like environment alters iDC properties and their response to HIV-1 infection. iDCs adopt an elongated morphology with increased deformability in 3D collagen at unaltered activation, differentiation, cytokine secretion, or responsiveness to LPS. While 3D collagen reduces HIV-1 particle uptake by iDCs, fusion efficiency is increased to elevate productive infection rates due to elevated cell surface exposure of the HIV-1-binding receptor DC-SIGN. In contrast, 3D collagen reduces HIV transfer to CD4 T cells from iDCs. iDC adaptations to 3D collagen include increased pro-inflammatory cytokine production and reduced antiviral gene expression in response to HIV-1 infection. Adhesion to a 2D collagen matrix is sufficient to increase iDC deformability, DC-SIGN exposure, and permissivity to HIV-1 infection. Thus, mechano-physical cues of 2D and 3D tissue-like collagen environments regulate iDC function and shape divergent roles during HIV-1 infection.
(© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE