Native and genetically inactivated pertussis toxins induce human dendritic cell maturation and synergize with lipopolysaccharide in promoting T helper type 1 responses.
The capacity of pertussis toxin (PT) to induce maturation and functional activities of human monocyte-derived dendritic cells (DCs) was investigated. Both native PT (nPT) and genetically detoxified PT (dPT) efficiently promoted expression on DCs of CD80, CD86, human leukocyte antigen-DR, and CD83 markers, alloreactive antigen presentation, and cytokine production, primarily interferon (IFN)-gamma. Although they did not affect interleukin (IL)-10 production by lipopolysaccharide (LPS)-stimulated DCs, both nPT and dPT strongly synergized with LPS for IL-12 production. PTs plus LPS-stimulated DCs secreted soluble factors fostering IFN-gamma but not IL-4 and IL-5 production by naive T cells. T helper type 1 (Th1) polarization was, as alloreactive antigen presentation, inhibited by anti-IL-12 monoclonal antibody. These findings support the notion that nPT, in addition to inducing specific immune response, is a potent Th1 adjuvant and that dPT fully preserves this adjuvanticity. The synergic interaction between PT and LPS in IL-12 production might be relevant for the mechanisms of vaccine-induced protection.
Ausiello
Clara M
CM
Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome 00161, Italy. ausiello@iss.it
Fedele
Giorgio
G
Urbani
Francesca
F
Lande
Roberto
R
Di Carlo
Beatrice
B
Cassone
Antonio
A
D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014121:Toxoids / Q000276:immunology / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D015703:Antigens, CD; D016207:Cytokines; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014121:Toxoids; D010566:Virulence Factors, Bordetella; C051093:pertussis toxoid; D037342:Pertussis Toxin