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Science 305 (5687): 1153-1157

Copyright © 2004 by the American Association for the Advancement of Science

Enhanced Dendritic Cell Antigen Capture via Toll-Like Receptor-Induced Actin Remodeling

Michele A. West,1* Robert P. A. Wallin,1,2,3* Stephen P. Matthews,1 Henrik G. Svensson,1 Rossana Zaru,1 Hans-Gustaf Ljunggren,3 Alan R. Prescott,1 Colin Watts1{dagger}

Abstract: 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.

1 Division of Cell Biology and Immunology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
2 Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
3 Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: c.watts{at}dundee.ac.uk

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B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells.
S. Radhakrishnan, E. Celis, and L. R. Pease (2005)
PNAS 102, 11438-11443
   Abstract »    Full Text »    PDF »
Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain.
L. M. Stuart, J. Deng, J. M. Silver, K. Takahashi, A. A. Tseng, E. J. Hennessy, R. A. B. Ezekowitz, and K. J. Moore (2005)
J. Cell Biol. 170, 477-485
   Abstract »    Full Text »    PDF »
Asparagine Deamidation Perturbs Antigen Presentation on Class II Major Histocompatibility Complex Molecules.
C. X. Moss, S. P. Matthews, D. J. Lamont, and C. Watts (2005)
J. Biol. Chem. 280, 18498-18503
   Abstract »    Full Text »    PDF »
Saturated and Polyunsaturated Fatty Acids Reciprocally Modulate Dendritic Cell Functions Mediated through TLR4.
A. R. Weatherill, J. Y. Lee, L. Zhao, D. G. Lemay, H. S. Youn, and D. H. Hwang (2005)
J. Immunol. 174, 5390-5397
   Abstract »    Full Text »    PDF »
Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2.
K. Takahashi, C. D.P. Rochford, and H. Neumann (2005)
J. Exp. Med. 201, 647-657
   Abstract »    Full Text »    PDF »

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