Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 3789K) PPT slides of all figures Supplemental Material Index Related biobytes podcast Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kool, M. Articles by Lambrecht, B. N. Search for Related Content PubMed PubMed Citation Articles by Kool, M. Articles by Lambrecht, B. N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB ALUMINUM SULFATE ALUM, POTASSIUM Related Collections Related In this Issue article Social Bookmarking                      What's this?

¹ Department of Pulmonary Medicine, Erasmus University Medical Centre, 3015 GD Rotterdam, Netherlands
² Laboratory of Immunoregulation, University Hospital Ghent, 9000 Ghent, Belgium
³ Weizmann Institute, Rehovot 76100, Israel

CORRESPONDENCE Bart N. Lambrecht: bart.lambrecht{at}ugent.be

Alum (aluminum hydroxide) is the most widely used adjuvant in human vaccines, but the mechanism of its adjuvanticity remains unknown. In vitro studies showed no stimulatory effects on dendritic cells (DCs). In the absence of adjuvant, Ag was taken up by lymph node (LN)–resident DCs that acquired soluble Ag via afferent lymphatics, whereas after injection of alum, Ag was taken up, processed, and presented by inflammatory monocytes that migrated from the peritoneum, thus becoming inflammatory DCs that induced a persistent Th2 response. The enhancing effects of alum on both cellular and humoral immunity were completely abolished when CD11c⁺ monocytes and DCs were conditionally depleted during immunization. Mechanistically, DC-driven responses were abolished in MyD88-deficient mice and after uricase treatment, implying the induction of uric acid. These findings suggest that alum adjuvant is immunogenic by exploiting "nature's adjuvant," the inflammatory DC through induction of the endogenous danger signal uric acid.

M. Kool, T. Soullié, H. Hammad, and B.N. Lambrecht contributed equally to this paper.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related In this Issue article

How alum works

Hema Bashyam
J. Exp. Med. 2008 205: 742. [Full Text] [PDF]

This article has been cited by other articles:

• Longhi, M. P., Trumpfheller, C., Idoyaga, J., Caskey, M., Matos, I., Kluger, C., Salazar, A. M., Colonna, M., Steinman, R. M. (2009). Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. JEM 206: 1589-1602 [Abstract] [Full Text]  
• Nakagome, K., Okunishi, K., Imamura, M., Harada, H., Matsumoto, T., Tanaka, R., Miyazaki, J.-i., Yamamoto, K., Dohi, M. (2009). IFN-{gamma} Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine. J. Immunol. 183: 209-220 [Abstract] [Full Text]  
• Wigren, M., Bengtsson, D., Duner, P., Olofsson, K., Bjorkbacka, H., Bengtsson, E., Fredrikson, G. N., Nilsson, J. (2009). Atheroprotective Effects of Alum Are Associated With Capture of Oxidized LDL Antigens and Activation of Regulatory T Cells. Circ. Res. 104: e62-e70 [Abstract] [Full Text]  
• Maue, A. C., Eaton, S. M., Lanthier, P. A., Sweet, K. B., Blumerman, S. L., Haynes, L. (2009). Proinflammatory Adjuvants Enhance the Cognate Helper Activity of Aged CD4 T Cells. J. Immunol. 182: 6129-6135 [Abstract] [Full Text]  
• Gasse, P., Riteau, N., Charron, S., Girre, S., Fick, L., Petrilli, V., Tschopp, J., Lagente, V., Quesniaux, V. F. J., Ryffel, B., Couillin, I. (2009). Uric Acid Is a Danger Signal Activating NALP3 Inflammasome in Lung Injury Inflammation and Fibrosis. Am. J. Respir. Crit. Care Med. 179: 903-913 [Abstract] [Full Text]  
• Boldizsar, F., Tarjanyi, O., Nemeth, P., Mikecz, K., Glant, T. T. (2009). Th1/Th17 polarization and acquisition of an arthritogenic phenotype in arthritis-susceptible BALB/c, but not in MHC-matched, arthritis-resistant DBA/2 mice. Int Immunol 21: 511-522 [Abstract] [Full Text]  
• Dalbeth, N., Merriman, T. (2009). Crystal ball gazing: new therapeutic targets for hyperuricaemia and gout. Rheumatology (Oxford) 48: 222-226 [Abstract] [Full Text]  
• Douagi, I., Gujer, C., Sundling, C., Adams, W. C., Smed-Sorensen, A., Seder, R. A., Karlsson Hedestam, G. B., Lore, K. (2009). Human B Cell Responses to TLR Ligands Are Differentially Modulated by Myeloid and Plasmacytoid Dendritic Cells. J. Immunol. 182: 1991-2001 [Abstract] [Full Text]  
• Mohr, E., Serre, K., Manz, R. A., Cunningham, A. F., Khan, M., Hardie, D. L., Bird, R., MacLennan, I. C. M. (2009). Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironments Where Plasmablasts Mature. J. Immunol. 182: 2113-2123 [Abstract] [Full Text]  
• Sharp, F. A., Ruane, D., Claass, B., Creagh, E., Harris, J., Malyala, P., Singh, M., O'Hagan, D. T., Petrilli, V., Tschopp, J., O'Neill, L. A. J., Lavelle, E. C. (2009). Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc. Natl. Acad. Sci. USA 106: 870-875 [Abstract] [Full Text]  
• Vultaggio, A., Nencini, F., Fitch, P. M., Fili, L., Maggi, L., Fanti, P., deVries, A., Beccastrini, E., Palandri, F., Manuelli, C., Bani, D., Giudizi, M. G., Guarna, A., Annunziato, F., Romagnani, S., Maggi, E., Howie, S. E. M., Parronchi, P. (2009). Modified Adenine (9-Benzyl-2-Butoxy-8-Hydroxyadenine) Redirects Th2-Mediated Murine Lung Inflammation by Triggering TLR7. J. Immunol. 182: 880-889 [Abstract] [Full Text]  
• Tonti, E., Galli, G., Malzone, C., Abrignani, S., Casorati, G., Dellabona, P. (2009). NKT-cell help to B lymphocytes can occur independently of cognate interaction. Blood 113: 370-376 [Abstract] [Full Text]  
• Bogaert, P., Tournoy, K. G., Naessens, T., Grooten, J. (2009). Where Asthma and Hypersensitivity Pneumonitis Meet and Differ: Noneosinophilic Severe Asthma. Am. J. Pathol. 174: 3-13 [Abstract] [Full Text]  
• Kaba, S. A., Price, A., Zhou, Z., Sundaram, V., Schnake, P., Goldman, I. F., Lal, A. A., Udhayakumar, V., Todd, C. W. (2008). Immune Responses of Mice with Different Genetic Backgrounds to Improved Multiepitope, Multitarget Malaria Vaccine Candidate Antigen FALVAC-1A. CVI 15: 1674-1683 [Abstract] [Full Text]  
• Zhou, W., Newcomb, D. C., Moore, M. L., Goleniewska, K., O'Neal, J. F., Peebles, R. S. Jr. (2008). Cyclooxygenase Inhibition during Allergic Sensitization Increases STAT6-Independent Primary and Memory Th2 Responses. J. Immunol. 181: 5360-5367 [Abstract] [Full Text]  
• Kool, M., Petrilli, V., De Smedt, T., Rolaz, A., Hammad, H., van Nimwegen, M., Bergen, I. M., Castillo, R., Lambrecht, B. N., Tschopp, J. (2008). Cutting Edge: Alum Adjuvant Stimulates Inflammatory Dendritic Cells through Activation of the NALP3 Inflammasome. J. Immunol. 181: 3755-3759 [Abstract] [Full Text]  
• Mosca, F., Tritto, E., Muzzi, A., Monaci, E., Bagnoli, F., Iavarone, C., O'Hagan, D., Rappuoli, R., De Gregorio, E. (2008). Molecular and cellular signatures of human vaccine adjuvants. Proc. Natl. Acad. Sci. USA 105: 10501-10506 [Abstract] [Full Text]  
• Li, H., Willingham, S. B., Ting, J. P.-Y., Re, F. (2008). Cutting Edge: Inflammasome Activation by Alum and Alum's Adjuvant Effect Are Mediated by NLRP3. J. Immunol. 181: 17-21 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS