Bordetella pertussis toxin induces the release of inflammatory cytokines and dendritic cell activation in whole blood: impaired responses in human newborns.
Bordetella pertussis toxin (PTX), a key component of acellular pertussis vaccines, is known to be endowed with adjuvant properties. In experiments designed to get insights into the interactions between PTX and circulating immune cells, we first observed that addition of PTX to adult whole blood induced the release of IL-12 and TNF-alpha as well as maturation of myeloid dendritic cells (DC). These effects were still present with a toxin mutant devoid of ADP-ribosyltransferase activity but not with a formaldehyde-inactivated toxin. These findings indicate that cytokine production and DC maturation require the intact structure of PTX but not its enzymatic activity. Secondly, studies on DC generated in vitro by culturing monocytes with IL-4 and GM-CSF showed that PTX directly stimulates MHC class II and costimulatory molecules up-regulation, cytokine synthesis and NF-kappa B activation. Finally, comparison of data obtained in adult vs. cord blood revealed deficient responses of neonatal DC to PTX. These data suggest new applications of PTX and PTX mutants as vaccine adjuvants.
Tonon
Sandrine
S
Laboratoire d'Immunologie Expérimentale, Université Libre de Bruxelles, Brussels, Belgium.
Goriely
Stanislas
S
Aksoy
Ezra
E
Pradier
Olivier
O
Del Giudice
Guiseppe
G
Trannoy
Emmanuelle
E
Willems
Fabienne
F
Goldman
Michel
M
De Wit
Dominique
D
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D018664:Interleukin-12 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology*
D016207:Cytokines; D016328:NF-kappa B; D018664:Interleukin-12; D037342:Pertussis Toxin