Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo

Munks, M.W., McKee, A.S., MacLeod, M.K.L. , Powell, R.L., Degen, J.L., Reisdorph, N.A., Kappler, J.W. and Marrack, P. (2010) Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo. Blood, 116(24), pp. 5191-5199. (doi: 10.1182/blood-2010-03-275529)

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Publisher's URL: http://dx.doi.org/10.1182/blood-2010-03-275529

Abstract

It has been recognized for nearly 80 years that insoluble aluminum salts are good immunologic adjuvants and that they form long-lived nodules in vivo. Nodule formation has long been presumed to be central for adjuvant activity by providing an antigen depot, but the composition and function of these nodules is poorly understood. We show here that aluminum salt nodules formed within hours of injection and contained the clotting protein fibrinogen. Fibrinogen was critical for nodule formation and required processing to insoluble fibrin by thrombin. DNase treatment partially disrupted the nodules, and the nodules contained histone H3 and citrullinated H3, features consistent with extracellular traps. Although neutrophils were not essential for nodule formation, CD11b+ cells were implicated. Vaccination of fibrinogen-deficient mice resulted in normal CD4 T-cell and antibody responses and enhanced CD8 T-cell responses, indicating that nodules are not required for aluminum's adjuvant effect. Moreover, the ability of aluminum salts to retain antigen in the body, the well-known depot effect, was unaffected by the absence of nodules. We conclude that aluminum adjuvants form fibrin-dependent nodules in vivo, that these nodules have properties of extracellular traps, and the nodules are not required for aluminum salts to act as adjuvants.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Macleod, Dr Megan
Authors: Munks, M.W., McKee, A.S., MacLeod, M.K.L., Powell, R.L., Degen, J.L., Reisdorph, N.A., Kappler, J.W., and Marrack, P.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020
Published Online:27 September 2010

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