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J. Exp. Med. 205 (4): 869-882

Copyright © 2008 by the Rockefeller University Press.

ARTICLE

Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells

Mirjam Kool1, Thomas Soullié1, Menno van Nimwegen1, Monique A.M. Willart1,2, Femke Muskens1, Steffen Jung3, Henk C. Hoogsteden1, Hamida Hammad1,2, , and Bart N. Lambrecht1,2

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

Abstract: 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.

Abbreviations used: Ag, antigen; Alum, aluminum hydroxide; CLN, cervical LN; DLN, draining LN; DT, diphteria toxin; DTR, DT receptor; ILN, inguinal LN; i.t., intratracheal; MLN, mediastinal LN; Tg, transgenic.

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

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Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)