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CX3CR1-Mediated Dendritic Cell Access to the Intestinal Lumen and Bacterial Clearance
Jan Hendrik Niess,1Stephan Brand,1Xiubin Gu,1Limor Landsman,4Steffen Jung,4,5Beth A. McCormick,2Jatin M. Vyas,3Marianne Boes,6Hidde L. Ploegh,6James G. Fox,7Dan R. Littman,5Hans-Christian Reinecker1*
Dendritic cells (DCs) and macrophages are critical to innateand adaptive immunity to the intestinal bacterial microbiota.Here, we identify a myeloid-derived mucosal DC in mice, whichpopulates the entire lamina propria of the small intestine.Lamina propria DCs were found to depend on the chemokine receptorCX3CR1 to form transepithelial dendrites, which enable the cellsto directly sample luminal antigens. CX3CR1 was also found tocontrol the clearance of entero-invasive pathogens by DCs. Thus,CX3CR1-dependent processes, which control host interactionsof specialized DCs with commensal and pathogenic bacteria, mayregulate immunological tolerance and inflammation.
1 Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. 2 Department of Pediatric Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. 3 Division of Infectious Diseases and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. 4 Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. 5 Molecular Pathogenesis Program, Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA. 6 Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. 7 Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 16-825A, Cambridge, MA 02139, USA.
* To whom correspondence should be addressed. E-mail: hans-christian_reinecker{at}hms.harvard.edu
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N. Eter, D. R. Engel, L. Meyer, H.-M. Helb, F. Roth, J. Maurer, F. G. Holz, and C. Kurts (2008)
Invest. Ophthalmol. Vis. Sci.
49, 3649-3658
|Abstract »|Full Text »|PDF »
Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues.
A. E. Cardona, M. E. Sasse, L. Liu, S. M. Cardona, M. Mizutani, C. Savarin, T. Hu, and R. M. Ransohoff (2008)
Blood
112, 256-263
|Abstract »|Full Text »|PDF »
Guanylyl Cyclase C-Induced Immunotherapeutic Responses Opposing Tumor Metastases Without Autoimmunity.
A. E. Snook, B. J. Stafford, P. Li, G. Tan, L. Huang, R. Birbe, S. Schulz, M. J. Schnell, M. Thakur, J. L. Rothstein, et al. (2008)
J Natl Cancer Inst
100, 950-961
|Abstract »|Full Text »|PDF »
A Novel Adenovirus Expressing Flt3 Ligand Enhances Mucosal Immunity by Inducing Mature Nasopharyngeal-Associated Lymphoreticular Tissue Dendritic Cell Migration.
S. Sekine, K. Kataoka, Y. Fukuyama, Y. Adachi, J. Davydova, M. Yamamoto, R. Kobayashi, K. Fujihashi, H. Suzuki, D. T. Curiel, et al. (2008)
J. Immunol.
180, 8126-8134
|Abstract »|Full Text »|PDF »
Immunology of the gut and liver: a love/hate relationship.
D H Adams, B Eksteen, and S M Curbishley (2008)
Gut
57, 838-848
|Full Text »|PDF »
Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse.
M. E. Wildenberg, C. G. van Helden-Meeuwsen, J. P. van de Merwe, C. Moreno, H. A. Drexhage, and M. A. Versnel (2008)
J. Leukoc. Biol.
83, 1194-1200
|Abstract »|Full Text »|PDF »
Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye.
J. Kezic, H. Xu, H. R. Chinnery, C. C. Murphy, and P. G. McMenamin (2008)
Invest. Ophthalmol. Vis. Sci.
49, 1599-1608
|Abstract »|Full Text »|PDF »
Peyer's Patches Are Required for Intestinal Immunoglobulin A Responses to Salmonella spp..
T. Hashizume, A. Togawa, T. Nochi, O. Igarashi, M.-N. Kweon, H. Kiyono, and M. Yamamoto (2008)
Infect. Immun.
76, 927-934
|Abstract »|Full Text »|PDF »
Microbe sampling by mucosal dendritic cells is a discrete, MyD88-independent stepin {Delta}invG S. Typhimurium colitis.
S. Hapfelmeier, A. J. Muller, B. Stecher, P. Kaiser, M. Barthel, K. Endt, M. Eberhard, R. Robbiani, C. A. Jacobi, M. Heikenwalder, et al. (2008)
J. Exp. Med.
205, 437-450
|Abstract »|Full Text »|PDF »
Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20.
E. E. Turer, R. M. Tavares, E. Mortier, O. Hitotsumatsu, R. Advincula, B. Lee, N. Shifrin, B. A. Malynn, and A. Ma (2008)
J. Exp. Med.
205, 451-464
|Abstract »|Full Text »|PDF »
CX3CR1 Deficiency Impairs Dendritic Cell Accumulation in Arterial Intima and Reduces Atherosclerotic Burden.
P. Liu, Y.-R. A. Yu, J. A. Spencer, A. E. Johnson, C. T. Vallanat, A. M. Fong, C. Patterson, and D. D. Patel (2008)
Arterioscler. Thromb. Vasc. Biol.
28, 243-250
|Abstract »|Full Text »|PDF »
Dose-Dependent Differential Regulation of Cytokine Secretion from Macrophages by Fractalkine.
N. Mizutani, T. Sakurai, T. Shibata, K. Uchida, J. Fujita, R. Kawashima, Y. I. Kawamura, N. Toyama-Sorimachi, T. Imai, and T. Dohi (2007)
J. Immunol.
179, 7478-7487
|Abstract »|Full Text »|PDF »
L. N. Fink, L. H. Zeuthen, H. R. Christensen, B. Morandi, H. Frokiaer, and G. Ferlazzo (2007)
Int. Immunol.
19, 1319-1327
|Abstract »|Full Text »|PDF »
Systemic Translocation of Salmonella enterica Serovar Dublin in Cattle Occurs Predominantly via Efferent Lymphatics in a Cell-Free Niche and Requires Type III Secretion System 1 (T3SS-1) but Not T3SS-2.
G. D. Pullinger, S. M. Paulin, B. Charleston, P. R. Watson, A. J. Bowen, F. Dziva, E. Morgan, B. Villarreal-Ramos, T. S. Wallis, and M. P. Stevens (2007)
Infect. Immun.
75, 5191-5199
|Abstract »|Full Text »|PDF »
The Role of Dendritic Cells in the Development of Acute Dextran Sulfate Sodium Colitis.
B. E. Berndt, M. Zhang, G.-H. Chen, G. B. Huffnagle, and J. Y. Kao (2007)
J. Immunol.
179, 6255-6262
|Abstract »|Full Text »|PDF »
Conventional dendritic cells regulate the outcome of colonic inflammation independently of T cells.
K. Abe, K. P. Nguyen, S. D. Fine, J.-H. Mo, C. Shen, S. Shenouda, M. Corr, S. Jung, J. Lee, L. Eckmann, et al. (2007)
PNAS
104, 17022-17027
|Abstract »|Full Text »|PDF »
The impact of cell-bound antigen transport on mucosal tolerance induction.
O. Pabst, G. Bernhardt, and R. Forster (2007)
J. Leukoc. Biol.
82, 795-800
|Abstract »|Full Text »|PDF »
The yin and yang of intestinal epithelial cells in controlling dendritic cell function.
I. D. Iliev, G. Matteoli, and M. Rescigno (2007)
J. Exp. Med.
204, 2253-2257
|Abstract »|Full Text »|PDF »
MyD88-mediated signals induce the bactericidal lectin RegIII{gamma} and protect mice against intestinal Listeria monocytogenes infection.
K. Brandl, G. Plitas, B. Schnabl, R. P. DeMatteo, and E. G. Pamer (2007)
J. Exp. Med.
204, 1891-1900
|Abstract »|Full Text »|PDF »
Murine Ccl2/Cx3cr1 Deficiency Results in Retinal Lesions Mimicking Human Age-Related Macular Degeneration.
J. Tuo, C. M. Bojanowski, M. Zhou, D. Shen, R. J. Ross, K. I. Rosenberg, D. J. Cameron, C. Yin, J. A. Kowalak, Z. Zhuang, et al. (2007)
Invest. Ophthalmol. Vis. Sci.
48, 3827-3836
|Abstract »|Full Text »|PDF »
Helicobacter bilis: bacterial provocateur orchestrates host immune responses to commensal flora in a model of inflammatory bowel disease.
Salmonella enterica serovar Typhimurium regulates intercellular junction proteins and facilitates transepithelial neutrophil and bacterial passage.
H. Kohler, T. Sakaguchi, B. P. Hurley, B. J. Kase, H.-C. Reinecker, and B. A. McCormick (2007)
Am J Physiol Gastrointest Liver Physiol
293, G178-G187
|Abstract »|Full Text »|PDF »
Lung Dendritic Cells Rapidly Mediate Anthrax Spore Entry through the Pulmonary Route.
A. Cleret, A. Quesnel-Hellmann, A. Vallon-Eberhard, B. Verrier, S. Jung, D. Vidal, J. Mathieu, and J.-N. Tournier (2007)
J. Immunol.
178, 7994-8001
|Abstract »|Full Text »|PDF »
Dendritic Cells and Macrophages Form a Transepithelial Network against Foreign Particulate Antigens.
F. Blank, B. Rothen-Rutishauser, and P. Gehr (2007)
Am. J. Respir. Cell Mol. Biol.
36, 669-677
|Abstract »|Full Text »|PDF »
The Chemokine Receptor CX3CR1 Mediates Homing of MHC class II-Positive Cells to the Normal Mouse Corneal Epithelium.
H. R. Chinnery, M. J. Ruitenberg, G. W. Plant, E. Pearlman, S. Jung, and P. G. McMenamin (2007)
Invest. Ophthalmol. Vis. Sci.
48, 1568-1574
|Abstract »|Full Text »|PDF »
Adhesin-dependent binding and uptake of Salmonella enterica serovar Typhimurium by dendritic cells.
A. Guo, M. A. Lasaro, J.-C. Sirard, J.-P. Kraehenbuhl, and D. M. Schifferli (2007)
Microbiology
153, 1059-1069
|Abstract »|Full Text »|PDF »
Bradyzoite-Specific Surface Antigen SRS9 Plays a Role in Maintaining Toxoplasma gondii Persistence in the Brain and in Host Control of Parasite Replication in the Intestine.
S.-K. Kim, A. Karasov, and J. C. Boothroyd (2007)
Infect. Immun.
75, 1626-1634
|Abstract »|Full Text »|PDF »
Solitary Intestinal Lymphoid Tissue Provides a Productive Port of Entry for Salmonella enterica Serovar Typhimurium.
S. Halle, D. Bumann, H. Herbrand, Y. Willer, S. Dahne, R. Forster, and O. Pabst (2007)
Infect. Immun.
75, 1577-1585
|Abstract »|Full Text »|PDF »
Cross-Talk between Probiotic Bacteria and the Host Immune System.
B. Corthesy, H. R. Gaskins, and A. Mercenier (2007)
J. Nutr.
137, 781S-790S
|Abstract »|Full Text »|PDF »
Murine CXCL14 Is Dispensable for Dendritic Cell Function and Localization within Peripheral Tissues.
S. Meuter, P. Schaerli, R. S. Roos, O. Brandau, M. R. Bosl, U. H. von Andrian, and B. Moser (2007)
Mol. Cell. Biol.
27, 983-992
|Abstract »|Full Text »|PDF »
Diverse and Potent Chemokine Production by Lung CD11bhigh Dendritic Cells in Homeostasis and in Allergic Lung Inflammation.
S. R. Beaty, C. E. Rose Jr., and S.-s. J. Sung (2007)
J. Immunol.
178, 1882-1895
|Abstract »|Full Text »|PDF »
Monocytes give rise to mucosal, but not splenic, conventional dendritic cells.
C. Varol, L. Landsman, D. K. Fogg, L. Greenshtein, B. Gildor, R. Margalit, V. Kalchenko, F. Geissmann, and S. Jung (2007)
J. Exp. Med.
204, 171-180
|Abstract »|Full Text »|PDF »
Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?.
Intervention of MAdCAM-1 or fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects.
S. Ueha, M. Murai, H. Yoneyama, M. Kitabatake, T. Imai, T. Shimaoka, S. Yonehara, S. Ishikawa, and K. Matsushima (2007)
J. Leukoc. Biol.
81, 176-185
|Abstract »|Full Text »|PDF »
Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells.
A. M. Durkan, R. T. Alexander, G.-Y. Liu, M. Rui, G. Femia, and L. A. Robinson (2007)
J. Am. Soc. Nephrol.
18, 74-83
|Abstract »|Full Text »|PDF »
Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement.
M. Chieppa, M. Rescigno, A. Y.C. Huang, and R. N. Germain (2006)
J. Exp. Med.
203, 2841-2852
|Abstract »|Full Text »|PDF »
CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells..
Accelerated Antigen Sampling and Transport by Airway Mucosal Dendritic Cells following Inhalation of a Bacterial Stimulus.
F. L. Jahnsen, D. H. Strickland, J. A. Thomas, I. T. Tobagus, S. Napoli, G. R. Zosky, D. J. Turner, P. D. Sly, P. A. Stumbles, and P. G. Holt (2006)
J. Immunol.
177, 5861-5867
|Abstract »|Full Text »|PDF »
Impact of Bronchial Epithelium on Dendritic Cell Migration and Function: Modulation by the Bacterial Motif KpOmpA.
M. Pichavant, S. Taront, P. Jeannin, L. Breuilh, A.-S. Charbonnier, C. Spriet, C. Fourneau, N. Corvaia, L. Heliot, A. Brichet, et al. (2006)
J. Immunol.
177, 5912-5919
|Abstract »|Full Text »|PDF »
Phagocytes Containing a Disease-Promoting Toll-Like Receptor/Nod Ligand Are Present in the Brain during Demyelinating Disease in Primates.
L. Visser, M.-J. Melief, D. van Riel, M. van Meurs, E. A. Sick, S. Inamura, J. J. Bajramovic, S. Amor, R. Q. Hintzen, L. A. Boven, et al. (2006)
Am. J. Pathol.
169, 1671-1685
|Abstract »|Full Text »|PDF »
CCR6 and CCL20: Partners in Intestinal Immunity and Lymphorganogenesis..
Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine.
P. D. Barnes, M. A. Bergman, J. Mecsas, and R. R. Isberg (2006)
J. Exp. Med.
203, 1591-1601
|Abstract »|Full Text »|PDF »
Murine norovirus: a model system to study norovirus biology and pathogenesis..
C. E. Wobus, L. B. Thackray, and H. W. Virgin IV (2006)
J. Virol.
80, 5104-5112
|Full Text »|PDF »
The Cysteine-Rich Region and Secreted Form of the Attachment G Glycoprotein of Respiratory Syncytial Virus Enhance the Cytotoxic T-Lymphocyte Response despite Lacking Major Histocompatibility Complex Class I-Restricted Epitopes..
A. Bukreyev, M. E. Serra, F. R. Laham, G. A. Melendi, S. R. Kleeberger, P. L. Collins, and F. P. Polack (2006)
J. Virol.
80, 5854-5861
|Abstract »|Full Text »|PDF »
Dendritic cells in pathogen recognition and induction of immune responses: a functional genomics approach.
M. Foti, F. Granucci, M. Pelizzola, O. Beretta, and P. Ricciardi-Castagnoli (2006)
J. Leukoc. Biol.
79, 913-916
|Abstract »|Full Text »|PDF »
The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system.
D. Huang, F.-D. Shi, S. Jung, G. C. Pien, J. Wang, T. P. Salazar-Mather, T. T. He, J. T. Weaver, H.-G. Ljunggren, C. A. Biron, et al. (2006)
FASEB J
20, 896-905
|Abstract »|Full Text »|PDF »
The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells.
N. Sanchez-Sanchez, L. Riol-Blanco, and J. L. Rodriguez-Fernandez (2006)
J. Immunol.
176, 5153-5159
|Abstract »|Full Text »|PDF »
Regulation of Intestinal Dendritic Cell Migration and Activation by Plasmacytoid Dendritic Cells, TNF-{alpha} and Type 1 IFNs after Feeding a TLR7/8 Ligand.
U. Yrlid, S. W. F. Milling, J. L. Miller, S. Cartland, C. D. Jenkins, and G. G. MacPherson (2006)
J. Immunol.
176, 5205-5212
|Abstract »|Full Text »|PDF »
ShiA Abrogates the Innate T-Cell Response to Shigella flexneri Infection.
IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration.
S. Brand, F. Beigel, T. Olszak, K. Zitzmann, S. T. Eichhorst, J.-M. Otte, H. Diepolder, A. Marquardt, W. Jagla, A. Popp, et al. (2006)
Am J Physiol Gastrointest Liver Physiol
290, G827-G838
|Abstract »|Full Text »|PDF »
Relationships between Distinct Blood Monocyte Subsets and Migrating Intestinal Lymph Dendritic Cells In Vivo under Steady-State Conditions.
U. Yrlid, C. D. Jenkins, and G. G. MacPherson (2006)
J. Immunol.
176, 4155-4162
|Abstract »|Full Text »|PDF »
TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium.
S. Chabot, J. S. Wagner, S. Farrant, and M. R. Neutra (2006)
J. Immunol.
176, 4275-4283
|Abstract »|Full Text »|PDF »
Modulation of Neonatal Microbial Recognition: TLR-Mediated Innate Immune Responses Are Specifically and Differentially Modulated by Human Milk.
E. LeBouder, J. E. Rey-Nores, A.-C. Raby, M. Affolter, K. Vidal, C. A. Thornton, and M. O. Labeta (2006)
J. Immunol.
176, 3742-3752
|Abstract »|Full Text »|PDF »
Lactic Acid Bacteria Inducing a Weak Interleukin-12 and Tumor Necrosis Factor Alpha Response in Human Dendritic Cells Inhibit Strongly Stimulating Lactic Acid Bacteria but Act Synergistically with Gram-Negative Bacteria..
L. H. Zeuthen, H. R. Christensen, and H. Frokiaer (2006)
Clin. Vaccine Immunol.
13, 365-375
|Abstract »|Full Text »|PDF »
Surfactant Sodium Lauryl Sulfate Enhances Skin Vaccination: Molecular Characterization via a Novel Technique using Ultrafiltration Capillaries and Mass Spectrometric Proteomics.
C.-M. Huang, C.-C. Wang, M. Kawai, S. Barnes, and C. A. Elmets (2006)
Mol. Cell. Proteomics
5, 523-532
|Abstract »|Full Text »|PDF »
Enterocyte TLR4 Mediates Phagocytosis and Translocation of Bacteria Across the Intestinal Barrier..
M. D. Neal, C. Leaphart, R. Levy, J. Prince, T. R. Billiar, S. Watkins, J. Li, S. Cetin, H. Ford, A. Schreiber, et al. (2006)
J. Immunol.
176, 3070-3079
|Abstract »|Full Text »|PDF »
Transepithelial Pathogen Uptake into the Small Intestinal Lamina Propria.
A. Vallon-Eberhard, L. Landsman, N. Yogev, B. Verrier, and S. Jung (2006)
J. Immunol.
176, 2465-2469
|Abstract »|Full Text »|PDF »
CCR7 Is Critically Important for Migration of Dendritic Cells in Intestinal Lamina Propria to Mesenteric Lymph Nodes.
M. H. Jang, N. Sougawa, T. Tanaka, T. Hirata, T. Hiroi, K. Tohya, Z. Guo, E. Umemoto, Y. Ebisuno, B.-G. Yang, et al. (2006)
J. Immunol.
176, 803-810
|Abstract »|Full Text »|PDF »
Virulence of Broad- and Narrow-Host-Range Salmonella enterica Serovars in the Streptomycin-Pretreated Mouse Model.
M. Suar, J. Jantsch, S. Hapfelmeier, M. Kremer, T. Stallmach, P. A. Barrow, and W.-D. Hardt (2006)
Infect. Immun.
74, 632-644
|Abstract »|Full Text »|PDF »
Network of dendritic cells within the muscular layer of the mouse intestine.
A. Flores-Langarica, S. Meza-Perez, J. Calderon-Amador, T. Estrada-Garcia, G. MacPherson, S. Lebecque, S. Saeland, R. M. Steinman, and L. Flores-Romo (2005)
PNAS
102, 19039-19044
|Abstract »|Full Text »|PDF »
Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different.
M. Rimoldi, M. Chieppa, P. Larghi, M. Vulcano, P. Allavena, and M. Rescigno (2005)
Blood
106, 2818-2826
|Abstract »|Full Text »|PDF »
TNF-{alpha}-Dependent and -Independent Maturation of Dendritic Cells and Recruited CD11cintCD11b+ Cells during Oral Salmonella Infection.
