Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Induction of Protective IgA by Intestinal Dendritic Cells Carrying Commensal Bacteria
Andrew J. Macpherson*, and
Therese Uhr
Abstract:
The enormous number of commensal bacteria in the lower intestineof vertebrates share abundant molecular patterns used for innateimmune recognition of pathogenic bacteria. We show that, eventhough commensals are rapidly killed by macrophages, intestinaldendritic cells (DCs) can retain small numbers of live commensalsfor several days. This allows DCs to selectively induce IgA,which helps protect against mucosal penetration by commensals.The commensal-loaded DCs are restricted to the mucosal immunecompartment by the mesenteric lymph nodes, which ensures thatimmune responses to commensal bacteria are induced locally,without potentially damaging systemic immune responses.
Institute of Experimental Immunology, Universitätsspital, CH8091 Zürich, Switzerland.
* To whom correspondence should be addressed. E-mail: amacpher{at}pathol.unizh.ch
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Jean-Pierre Kraehenbuhl and Max Corbett (12 March 2004) Science303 (5664), 1624.
[DOI: 10.1126/science.1096222] |Summary »|Full Text »|PDF »
A Rice-Based Oral Cholera Vaccine Induces Macaque-Specific Systemic Neutralizing Antibodies but Does Not Influence Pre-Existing Intestinal Immunity.
T. Nochi, Y. Yuki, Y. Katakai, H. Shibata, D. Tokuhara, M. Mejima, S. Kurokawa, Y. Takahashi, U. Nakanishi, F. Ono, et al. (2009)
J. Immunol.
183, 6538-6544
|Abstract »|Full Text »|PDF »
Toll-like Receptors 3, 4, and 7 Are Expressed in the Enteric Nervous System and Dorsal Root Ganglia.
I. Barajon, G. Serrao, F. Arnaboldi, E. Opizzi, G. Ripamonti, A. Balsari, and C. Rumio (2009)
J. Histochem. Cytochem.
57, 1013-1023
|Abstract »|Full Text »|PDF »
Mesenteric Lymph Nodes Confine Dendritic Cell-Mediated Dissemination of Salmonella enterica Serovar Typhimurium and Limit Systemic Disease in Mice.
S. Voedisch, C. Koenecke, S. David, H. Herbrand, R. Forster, M. Rhen, and O. Pabst (2009)
Infect. Immun.
77, 3170-3180
|Abstract »|Full Text »|PDF »
Innate and Adaptive Immunity Cooperate Flexibly to Maintain Host-Microbiota Mutualism.
E. Slack, S. Hapfelmeier, B. Stecher, Y. Velykoredko, M. Stoel, M. A. E. Lawson, M. B. Geuking, B. Beutler, T. F. Tedder, W.-D. Hardt, et al. (2009)
Science
325, 617-620
|Abstract »|Full Text »|PDF »
Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge.
M. Mohamadzadeh, T. Duong, S. J. Sandwick, T. Hoover, and T. R. Klaenhammer (2009)
PNAS
106, 4331-4336
|Abstract »|Full Text »|PDF »
Hyporesponsiveness of Intestinal Dendritic Cells to TLR Stimulation Is Limited to TLR4.
V. Cerovic, C. D. Jenkins, A. G. C. Barnes, S. W. F. Milling, G. G. MacPherson, and L. S. Klavinskis (2009)
J. Immunol.
182, 2405-2415
|Abstract »|Full Text »|PDF »
Regulatory T Cells Modulate Staphylococcal Enterotoxin B-Induced Effector T-Cell Activation and Acceleration of Colitis.
A. Heriazon, P. Zhou, R. Borojevic, K. Foerster, C. J. Streutker, T. Ng, and K. Croitoru (2009)
Infect. Immun.
77, 707-713
|Abstract »|Full Text »|PDF »
CD83+CCR7- Dendritic Cells Accumulate in the Subepithelial Dome and Internalize Translocated Escherichia coli HB101 in the Peyer's Patches of Ileal Crohn's Disease.
S. Y. Salim, M. A. Silva, A. V. Keita, M. Larsson, P. Andersson, K.-E. Magnusson, M. H. Perdue, and J. D. Soderholm (2009)
Am. J. Pathol.
174, 82-90
|Abstract »|Full Text »|PDF »
Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface.
S. Vaishnava, C. L. Behrendt, A. S. Ismail, L. Eckmann, and L. V. Hooper (2008)
PNAS
105, 20858-20863
|Abstract »|Full Text »|PDF »
Genes and Molecules of Lactobacilli Supporting Probiotic Action.
S. Lebeer, J. Vanderleyden, and S. C. J. De Keersmaecker (2008)
Microbiol. Mol. Biol. Rev.
72, 728-764
|Abstract »|Full Text »|PDF »
Bacterial-mucosal interactions in inflammatory bowel disease--an alliance gone bad.
M. Chichlowski and L. P. Hale (2008)
Am J Physiol Gastrointest Liver Physiol
295, G1139-G1149
|Abstract »|Full Text »|PDF »
Epithelial and Mesenchymal Cells in the Bovine Colonic Mucosa Differ in Their Responsiveness to Escherichia coli Shiga Toxin 1.
I. Stamm, M. Mohr, P. S. Bridger, E. Schropfer, M. Konig, W. C. Stoffregen, E. A. Dean-Nystrom, G. Baljer, and C. Menge (2008)
Infect. Immun.
76, 5381-5391
|Abstract »|Full Text »|PDF »
Deficiency of Indoleamine 2,3-Dioxygenase Enhances Commensal-Induced Antibody Responses and Protects against Citrobacter rodentium-Induced Colitis.
L. Harrington, C. V. Srikanth, R. Antony, S. J. Rhee, A. L. Mellor, H. N. Shi, and B. J. Cherayil (2008)
Infect. Immun.
76, 3045-3053
|Abstract »|Full Text »|PDF »
Viral Double-Stranded RNA Triggers Ig Class Switching by Activating Upper Respiratory Mucosa B Cells through an Innate TLR3 Pathway Involving BAFF.
W. Xu, P. A. Santini, A. J. Matthews, A. Chiu, A. Plebani, B. He, K. Chen, and A. Cerutti (2008)
J. Immunol.
181, 276-287
|Abstract »|Full Text »|PDF »
Identification of Genes Associated with the Long-Gut-Persistence Phenotype of the Probiotic Lactobacillus johnsonii Strain NCC533 Using a Combination of Genomics and Transcriptome Analysis.
E. Denou, R. D. Pridmore, B. Berger, J.-M. Panoff, F. Arigoni, and H. Brussow (2008)
J. Bacteriol.
190, 3161-3168
|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 »
Microbial Imprinting in Gut Development and Health.
J. J. Dibner, J. D. Richards, and C. D. Knight (2008)
J. Appl. Poult. Res.
17, 174-188
|Abstract »|Full Text »|PDF »
Host Transmission of Salmonella enterica Serovar Typhimurium Is Controlled by Virulence Factors and Indigenous Intestinal Microbiota.
T. D. Lawley, D. M. Bouley, Y. E. Hoy, C. Gerke, D. A. Relman, and D. M. Monack (2008)
Infect. Immun.
76, 403-416
|Abstract »|Full Text »|PDF »
Secretory IgA Mediates Bacterial Translocation to Dendritic Cells in Mouse Peyer's Patches with Restriction to Mucosal Compartment.
A. Daley, R. Randall, M. Darsley, N. Choudhry, N. Thomas, I. R Sanderson, N. M Croft, and P. Kelly (2007)
Gut
56, 1550-1556
|Abstract »|Full Text »|PDF »
Survival of Chlamydia muridarum within Dendritic Cells.
J. Rey-Ladino, X. Jiang, B. R. Gabel, C. Shen, and R. C. Brunham (2007)
Infect. Immun.
75, 3707-3714
|Abstract »|Full Text »|PDF »
Interactions between epithelial cells and leukocytes in immunity and tissue homeostasis.
Systemic CD8 T-Cell Memory Response to a Salmonella Pathogenicity Island 2 Effector Is Restricted to Salmonella enterica Encountered in the Gastrointestinal Mucosa.
J. Jones-Carson, B. D. McCollister, E. T. Clambey, and A. Vazquez-Torres (2007)
Infect. Immun.
75, 2708-2716
|Abstract »|Full Text »|PDF »
Proposed Model: Mechanisms of Immunomodulation Induced by Probiotic Bacteria.
C. M. Galdeano, A. de Moreno de LeBlanc, G. Vinderola, M. E. B. Bonet, and G. Perdigon (2007)
Clin. Vaccine Immunol.
14, 485-492
|Full Text »|PDF »
In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut.
J. F. Rawls, M. A. Mahowald, A. L. Goodman, C. M. Trent, and J. I. Gordon (2007)
PNAS
104, 7622-7627
|Abstract »|Full Text »|PDF »
Oral Treatment with Live Lactobacillus reuteri Inhibits the Allergic Airway Response in Mice.
P. Forsythe, M. D. Inman, and J. Bienenstock (2007)
Am. J. Respir. Crit. Care Med.
175, 561-569
|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 »
Bacterial Imprinting of the Neonatal Immune System: Lessons From Maternal Cells?.
P. F. Perez, J. Dore, M. Leclerc, F. Levenez, J. Benyacoub, P. Serrant, I. Segura-Roggero, E. J. Schiffrin, and A. Donnet-Hughes (2007)
Pediatrics
119, e724-e732
|Abstract »|Full Text »|PDF »
Secretory Antibody Formation: Conserved Binding Interactions between J Chain and Polymeric Ig Receptor from Humans and Amphibians.
R. Braathen, V. S. Hohman, P. Brandtzaeg, and F.-E. Johansen (2007)
J. Immunol.
178, 1589-1597
|Abstract »|Full Text »|PDF »
Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?.
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 »
Gut IgA Class Switch Recombination in the Absence of CD40 Does Not Occur in the Lamina Propria and Is Independent of Germinal Centers.
P. Bergqvist, E. Gardby, A. Stensson, M. Bemark, and N. Y. Lycke (2006)
J. Immunol.
177, 7772-7783
|Abstract »|Full Text »|PDF »
Induction of Tolerance to Innocuous Inhaled Antigen Relies on a CCR7-Dependent Dendritic Cell-Mediated Antigen Transport to the Bronchial Lymph Node.
G. Hintzen, L. Ohl, M.-L. del Rio, J.-I. Rodriguez-Barbosa, O. Pabst, J. R. Kocks, J. Krege, S. Hardtke, and R. Forster (2006)
J. Immunol.
177, 7346-7354
|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 »
Probiotics stimulate production of natural antibodies in chickens..
H. R. Haghighi, J. Gong, C. L. Gyles, M. A. Hayes, H. Zhou, B. Sanei, J. R. Chambers, and S. Sharif (2006)
Clin. Vaccine Immunol.
13, 975-980
|Abstract »|Full Text »|PDF »
Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice.
M.-E. Dumas, R. H. Barton, A. Toye, O. Cloarec, C. Blancher, A. Rothwell, J. Fearnside, R. Tatoud, V. Blanc, J. C. Lindon, et al. (2006)
PNAS
103, 12511-12516
|Abstract »|Full Text »|PDF »
Peyer's Patches Are Required for the Induction of Rapid Th1 Responses in the Gut and Mesenteric Lymph Nodes during an Enteric Infection..
The Front Line of Enteric Host Defense against Unwelcome Intrusion of Harmful Microorganisms: Mucins, Antimicrobial Peptides, and Microbiota.
V. Lievin-Le Moal and A. L. Servin (2006)
Clin. Microbiol. Rev.
19, 315-337
|Abstract »|Full Text »|PDF »
Differential cytokine response from dendritic cells to commensal and pathogenic bacteria in different lymphoid compartments in humans.
L. O'Mahony, L. O'Callaghan, J. McCarthy, D. Shilling, P. Scully, S. Sibartie, E. Kavanagh, W. O. Kirwan, H. P. Redmond, J. K. Collins, et al. (2006)
Am J Physiol Gastrointest Liver Physiol
290, G839-G845
|Abstract »|Full Text »|PDF »
Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells.
T. Worbs, U. Bode, S. Yan, M. W. Hoffmann, G. Hintzen, G. Bernhardt, R. Forster, and O. Pabst (2006)
J. Exp. Med.
203, 519-527
|Abstract »|Full Text »|PDF »
Mesenteric lymph nodes at the center of immune anatomy.
Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease.
J O Lindsay, K Whelan, A J Stagg, P Gobin, H O Al-Hassi, N Rayment, M A Kamm, S C Knight, and A Forbes (2006)
Gut
55, 348-355
|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 »
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 »
Bugging the intestinal response to radiation.
R. R. Weichselbaum (2005)
PNAS
102, 13363-13364
|Full Text »|PDF »
From The Cover: Microbial regulation of intestinal radiosensitivity.
Concurrent Infection with an Intestinal Helminth Parasite Impairs Host Resistance to Enteric Citrobacter rodentium and Enhances Citrobacter-Induced Colitis in Mice.
C.-C. Chen, S. Louie, B. McCormick, W. A. Walker, and H. N. Shi (2005)
Infect. Immun.
73, 5468-5481
|Abstract »|Full Text »|PDF »
Probiotics as mainstream allergy therapy?.
S H Murch (2005)
Arch. Dis. Child.
90, 881-882
|Full Text »|PDF »
The mucosal immune system: from control of inflammation to protection against infections.
D. Kaiserlian, N. Cerf-Bensussan, and A. Hosmalin (2005)
J. Leukoc. Biol.
78, 311-318
|Abstract »|Full Text »|PDF »
Enterococcus faecium SF68 Enhances the Immune Response to Giardia intestinalis in Mice.
J. Benyacoub, P. F. Perez, F. Rochat, K. Y. Saudan, G. Reuteler, N. Antille, M. Humen, G. L. De Antoni, C. Cavadini, S. Blum, et al. (2005)
J. Nutr.
135, 1171-1176
|Abstract »|Full Text »|PDF »
Differential Lysosomal Proteolysis in Antigen-Presenting Cells Determines Antigen Fate.
L. Delamarre, M. Pack, H. Chang, I. Mellman, and E. S. Trombetta (2005)
Science
307, 1630-1634
|Abstract »|Full Text »|PDF »
Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Pathophysiological basis and prospects for probiotic therapy in inflammatory bowel disease.
The Salmonella Pathogenicity Island (SPI)-2 and SPI-1 Type III Secretion Systems Allow Salmonella Serovar typhimurium to Trigger Colitis via MyD88-Dependent and MyD88-Independent Mechanisms.
S. Hapfelmeier, B. Stecher, M. Barthel, M. Kremer, A. J. Muller, M. Heikenwalder, T. Stallmach, M. Hensel, K. Pfeffer, S. Akira, et al. (2005)
J. Immunol.
174, 1675-1685
|Abstract »|Full Text »|PDF »
CX3CR1-Mediated Dendritic Cell Access to the Intestinal Lumen and Bacterial Clearance.
J. H. Niess, S. Brand, X. Gu, L. Landsman, S. Jung, B. A. McCormick, J. M. Vyas, M. Boes, H. L. Ploegh, J. G. Fox, et al. (2005)
Science
307, 254-258
|Abstract »|Full Text »|PDF »
Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury.
S. L. Pull, J. M. Doherty, J. C. Mills, J. I. Gordon, and T. S. Stappenbeck (2005)
PNAS
102, 99-104
|Abstract »|Full Text »|PDF »
Food allergy in irritable bowel syndrome: new facts and old fallacies.
