Department of Infectious Diseases, Integrative Virology, CIID, University Hospital Heidelberg, Heidelberg, Germany.
Biophysical Engineering Group, Max Planck Institute for Medical Research, Heidelberg, Germany.
EMBO Rep. 2023 Jun 5;24(6):e56818. doi: 10.15252/embr.202356818. Epub 2023 Apr 12.
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.
未成熟树突状细胞 (iDCs) 在体内具有不同细胞和细胞外基质密度的微环境中迁移，并有助于 HIV-1 的传播和抗病毒免疫反应的产生。在这里，我们发现与标准的 2D 悬浮培养相比，3D 胶原作为组织样环境会改变 iDC 的特性及其对 HIV-1 感染的反应。iDC 在未改变激活、分化、细胞因子分泌或对 LPS 反应的情况下，在 3D 胶原中呈现出拉长的形态，并且变形能力增强。虽然 3D 胶原减少了 iDC 对 HIV-1 颗粒的摄取，但由于 HIV-1 结合受体 DC-SIGN 的细胞表面暴露增加，融合效率增加，从而提高了产生活感染率。相比之下，3D 胶原减少了 iDC 向 CD4 T 细胞的 HIV 转移。iDC 对 3D 胶原的适应包括增加促炎细胞因子的产生和减少对 HIV-1 感染的抗病毒基因表达。与 2D 胶原基质的黏附足以增加 iDC 的变形能力、DC-SIGN 的暴露以及对 HIV-1 感染的易感性。因此，2D 和 3D 组织样胶原环境的力学物理线索调节 iDC 的功能，并在 HIV-1 感染期间形成不同的作用。
