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.
Division of Cell Biology and Immunology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Michele A
MA
West
Robert P A
RP
Wallin
Stephen P
SP
Matthews
Henrik G
HG
Svensson
Rossana
R
Zaru
Hans-Gustaf
HG
Ljunggren
Alan R
AR
Prescott
Colin
C
Watts
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