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Science 304 (5673): 1014-1018

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

Regulation of Phagosome Maturation by Signals from Toll-Like Receptors

J. Magarian Blander, and Ruslan Medzhitov*

Abstract: In higher metazoans, phagocytosis is essential in host defense against microbial pathogens and in clearance of apoptotic cells. Both microbial and apoptotic cells are delivered on a common route from phagosomes to lysosomes for degradation. Here, we found that activation of the Toll-like receptor (TLR) signaling pathway by bacteria, but not apoptotic cells, regulated phagocytosis at multiple steps including internalization and phagosome maturation. Phagocytosis of bacteria was impaired in the absence of TLR signaling. Two modes of phagosome maturation were observed, constitutive and inducible; their differential engagement depended on the ability of the cargo to trigger TLR signaling.

Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

* To whom correspondence should be addressed. E-mail: ruslan.medzhitov{at}yale.edu

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J. Immunol. 181, 7562-7570
   Abstract »    Full Text »    PDF »
Phagocytosis and antigen presentation: a partnership initiated by Toll-like receptors.
J M. Blander (2008)
Ann Rheum Dis 67, iii44-iii49
   Abstract »    Full Text »    PDF »
CD14 Impairs Host Defense against Gram-Negative Sepsis Caused by Burkholderia pseudomallei in Mice.
W. J. Wiersinga, A. F. de Vos, C. W. Wieland, M. Leendertse, J. J. T. H. Roelofs, and T. van der Poll (2008)
The Journal of Infectious Disease 198, 1388-1397
   Abstract »    Full Text »    PDF »
{beta}2-Integrin-induced p38 MAPK Activation Is a Key Mediator in the CD14/TLR4/MD2-dependent Uptake of Lipopolysaccharide by Hepatocytes.
M. J. Scott and T. R. Billiar (2008)
J. Biol. Chem. 283, 29433-29446
   Abstract »    Full Text »    PDF »
LspA inactivation in Mycobacterium tuberculosis results in attenuation without affecting phagosome maturation arrest.
S. K. Rampini, P. Selchow, C. Keller, S. Ehlers, E. C. Bottger, and P. Sander (2008)
Microbiology 154, 2991-3001
   Abstract »    Full Text »    PDF »
Importance of TLR2 in Early Innate Immune Response to Acute Pulmonary Infection with Porphyromonas gingivalis in Mice.
G. Hajishengallis, M. Wang, G. J. Bagby, and S. Nelson (2008)
J. Immunol. 181, 4141-4149
   Abstract »    Full Text »    PDF »
TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent.
M. A. West, A. R. Prescott, K. M. Chan, Z. Zhou, S. Rose-John, J. Scheller, and C. Watts (2008)
J. Cell Biol. 182, 993-1005
   Abstract »    Full Text »    PDF »
NF-{kappa}B Activation Controls Phagolysosome Fusion-Mediated Killing of Mycobacteria by Macrophages.
M. G. Gutierrez, B. B. Mishra, L. Jordao, E. Elliott, E. Anes, and G. Griffiths (2008)
J. Immunol. 181, 2651-2663
   Abstract »    Full Text »    PDF »
Incorporation of Mycobacterium tuberculosis Lipoarabinomannan into Macrophage Membrane Rafts Is a Prerequisite for the Phagosomal Maturation Block.
A. Welin, M. E. Winberg, H. Abdalla, E. Sarndahl, B. Rasmusson, O. Stendahl, and M. Lerm (2008)
Infect. Immun. 76, 2882-2887
   Abstract »    Full Text »    PDF »
Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling.
W. Cao, C. Bao, E. Padalko, and C. J. Lowenstein (2008)
J. Exp. Med. 205, 1491-1503
   Abstract »    Full Text »    PDF »
Distinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis of Borrelia burgdorferi and Cytokine Induction.
O. S. Shin, R. R. Isberg, S. Akira, S. Uematsu, A. K. Behera, and L. T. Hu (2008)
Infect. Immun. 76, 2341-2351
   Abstract »    Full Text »    PDF »
Immune Recognition of Streptococcus pyogenes by Dendritic Cells.
T. G. Loof, O. Goldmann, and E. Medina (2008)
Infect. Immun. 76, 2785-2792
   Abstract »    Full Text »    PDF »
Macrophage Proinflammatory Response to Francisella tularensis Live Vaccine Strain Requires Coordination of Multiple Signaling Pathways.
L. E. Cole, A. Santiago, E. Barry, T. J. Kang, K. A. Shirey, Z. J. Roberts, K. L. Elkins, A. S. Cross, and S. N. Vogel (2008)
J. Immunol. 180, 6885-6891
   Abstract »    Full Text »    PDF »
Phagocytosis and intracellular killing of MD-2 opsonized Gram-negative bacteria depend on TLR4 signaling.
V. Jain, A. Halle, K. A. Halmen, E. Lien, M. Charrel-Dennis, S. Ram, D. T. Golenbock, and A. Visintin (2008)
Blood 111, 4637-4645
   Abstract »    Full Text »    PDF »
TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity.
V. Lampropoulou, K. Hoehlig, T. Roch, P. Neves, E. C. Gomez, C. H. Sweenie, Y. Hao, A. A. Freitas, U. Steinhoff, S. M. Anderton, et al. (2008)
J. Immunol. 180, 4763-4773
   Abstract »    Full Text »    PDF »
TLR2-Dependent MyD88 Signaling Contributes to Early Host Defense in Murine Enterococcus faecium Peritonitis.
M. Leendertse, R. J. L. Willems, I. A. J. Giebelen, P. S. van den Pangaart, W. J. Wiersinga, A. F. de Vos, S. Florquin, M. J. M. Bonten, and T. van der Poll (2008)
J. Immunol. 180, 4865-4874
   Abstract »    Full Text »    PDF »

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