Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells

Frontiers in Immunology
Céline CougouleIsabelle Maridonneau-Parini

Abstract

Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo, or in collagen matrices in vitro. However, the mechanisms of 3D migration used by human immature DC (iDC) are still poorly characterized. Here, we reveal that human monocyte-derived DC are able to use two migration modes in 3D. In porous matrices of fibrillar collagen I, iDC adopted the amoeboid migration mode. In dense matrices of gelled collagen I or Matrigel, iDC used the protease-dependent, ROCK-independent mesenchymal migration mode. Upon TLR4 activation by LPS, mDC-LPS lose the capacity to form podosomes and degrade the matrix along with impaired mesenchymal migration. TLR2 activation by Pam3CSK4 resulted in DC maturation, podosome maintenance, and efficient mesenchymal migration. Under all these conditions, when DC used the mese...Continue Reading

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Citations

May 6, 2019·Cancers·Rafael PeláezIgnacio M Larrayoz
Dec 15, 2019·Journal of Cell Science·Koen van den DriesRenaud Poincloux
Jan 23, 2020·Viruses·Linda GroscheChristiane Silke Heilingloh
Jun 20, 2020·Journal of Leukocyte Biology·Mariana M S Oliveira, Lisa S Westerberg
Feb 10, 2021·Journal of Cell Science·Sara Tur-Gracia, Narcisa Martinez-Quiles
Jul 13, 2021·Experimental Biology and Medicine·Brian J Kwee, Kyung E Sung

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
flow cytometry
Scanning electron microscopy

Software Mentioned

FlowJo
GraphPad
TreeStar
ImageJ
GraphPad Prism

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