Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling.
Microbial products are sensed through Toll-like receptors (TLRs) and trigger a program of dendritic cell (DC) maturation that enables DCs to activate T cells. Although an accepted hallmark of this response is eventual down-regulation of DC endocytic capacity, we show that TLR ligands first acutely stimulate antigen macropinocytosis, leading to enhanced presentation on class I and class II major histocompatibility complex molecules. Simultaneously, actin-rich podosomes disappear, which suggests a coordinated redeployment of actin to fuel endocytosis. These reciprocal changes are transient and require p38 and extracellular signal-regulated kinase activation. Thus, the DC actin cytoskeleton can be rapidly mobilized in response to innate immune stimuli to enhance antigen capture and presentation.
West
Michele A
MA
Division of Cell Biology and Immunology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Wallin
Robert P A
RP
Matthews
Stephen P
SP
Svensson
Henrik G
HG
Zaru
Rossana
R
Ljunggren
Hans-Gustaf
HG
Prescott
Alan R
AR
Watts
Colin
C
D000199:Actins / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D004705:Endocytosis; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010873:Pinocytosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors
D000199:Actins; D000941:Antigens; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D020928:Mitogen-Activated Protein Kinases