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

© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

EMBO reports - 24(2023), 6 vom: 05. Juni, Seite e56818

Sprache:

Englisch

Beteiligte Personen:

Gallucci, Lara [VerfasserIn]
Abele, Tobias [VerfasserIn]
Fronza, Raffaele [VerfasserIn]
Stolp, Bettina [VerfasserIn]
Laketa, Vibor [VerfasserIn]
Sid Ahmed, Samy [VerfasserIn]
Flemming, Annica [VerfasserIn]
Müller, Barbara [VerfasserIn]
Göpfrich, Kerstin [VerfasserIn]
Fackler, Oliver T [VerfasserIn]

Links:

Volltext

Themen:

3D culture
9007-34-5
Antiviral Agents
Collagen
Cytokines
HIV
Immature dendritic cells
Innate immune recognition
Journal Article
Real-time deformability cytometry (RT-DC)
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 06.06.2023

Date Revised 13.06.2023

published: Print-Electronic

GEO: GSE218367

Citation Status MEDLINE

doi:

10.15252/embr.202356818

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM355471302