Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo

Michael Munks, Amy S. McKee, Megan K. MacLeod, Roger L. Powell, Jay L. Degen, Nichole A. Reisdorph, John W. Kappler, Philippa Marrack

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5191-5199
Number of pages9
JournalBlood
Volume116
Issue number24
DOIs
StatePublished - Dec 9 2010
Externally publishedYes

Fingerprint

Fibrin
Aluminum
Salts
Fibrinogen
T-cells
T-Lymphocytes
Antigens
Immunologic Adjuvants
Deoxyribonucleases
Thrombin
Histones
Antibody Formation
Extracellular Traps
Vaccination
Neutrophils
Injections
Antibodies
Processing
Chemical analysis
Proteins

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

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

Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo. / Munks, Michael; McKee, Amy S.; MacLeod, Megan K.; Powell, Roger L.; Degen, Jay L.; Reisdorph, Nichole A.; Kappler, John W.; Marrack, Philippa.

In: Blood, Vol. 116, No. 24, 09.12.2010, p. 5191-5199.

Research output: Contribution to journalArticle

Munks, M, McKee, AS, MacLeod, MK, Powell, RL, Degen, JL, Reisdorph, NA, Kappler, JW & Marrack, P 2010, 'Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo', Blood, vol. 116, no. 24, pp. 5191-5199. https://doi.org/10.1182/blood-2010-03-275529
Munks M, McKee AS, MacLeod MK, Powell RL, Degen JL, Reisdorph NA et al. Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo. Blood. 2010 Dec 9;116(24):5191-5199. https://doi.org/10.1182/blood-2010-03-275529
Munks, Michael ; McKee, Amy S. ; MacLeod, Megan K. ; Powell, Roger L. ; Degen, Jay L. ; Reisdorph, Nichole A. ; Kappler, John W. ; Marrack, Philippa. / Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo. In: Blood. 2010 ; Vol. 116, No. 24. pp. 5191-5199.
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