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

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.

Automated summary

Compared to 2D suspension cultures, 3D collagen as a tissue-like environment alters immature dendritic cell (iDC) properties and their response to HIV-1 infection. iDCs in 3D collagen have an elongated morphology with increased deformability, reduced HIV-1 particle uptake, and increased fusion efficiency. Adhesion to a 2D collagen matrix is sufficient to increase iDC deformability, HIV-1 receptor exposure, and permissivity to infection. These findings suggest that mechano-physical cues of 2D and 3D collagen environments regulate iDC function and shape divergent roles during HIV-1 infection.