Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type.
Aluminum hydroxide (AlOOH) has been used for many years as a vaccine adjuvant, but little is known about its mechanism of action. We investigated in this study the in vitro effect of aluminum hydroxide adjuvant on isolated macrophages. We showed that AlOOH-stimulated macrophages contain large and persistent intracellular crystalline inclusions, a characteristic property of muscle infiltrated macrophages described in animal models of vaccine injection, as well as in the recently described macrophagic myofasciitis (MMF) histological reaction in humans. AlOOH-loaded macrophages exhibited phenotypical and functional modifications, as they expressed the classical markers of myeloid dendritic cells (HLA-DR(high)/CD86(high)/CD83(+)/CD1a(-)/CD14(-)) and displayed potent ability to induce MHC-II-restricted antigen specific memory responses, but kept a macrophage morphology. This suggests a key role of macrophages, in the reaction to AlOOH-adjuvanted vaccines and these mature antigen-presenting macrophages may therefore be of particular importance in the establishment of memory responses and in vaccination mechanisms leading to long-lasting protection.
Rimaniol
Anne-Cécile
AC
SPI-BIO, c/o Service de Neurovirologie, 92265 Fontenay-aux-Roses Cedex, France.
Gras
Gabriel
G
Verdier
François
F
Capel
Francis
F
Grigoriev
Vladimir B
VB
Porcheray
Fabrice
F
Sauzeat
Elisabeth
E
Fournier
Jean-Guy
JG
Clayette
Pascal
P
Siegrist
Claire-Anne
CA
Dormont
Dominique
D
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D015703:Antigens, CD; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis; D008854:Microscopy, Electron; D010641:Phenotype; D000097802:CD83 Antigen
D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide; D015703:Antigens, CD; D016207:Cytokines; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000097802:CD83 Antigen