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1 August 2002

Volume 186, Number 3
The Journal of Infectious Diseases 2002;186:351–360
© 2002 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2002/18603-0007$15.00
DOI: 10.1086/341510

Native and Genetically Inactivated Pertussis Toxins Induce Human Dendritic Cell Maturation and Synergize with Lipopolysaccharide in Promoting T Helper Type 1 Responses

Clara M. Ausiello,

Giorgio Fedele,

Francesca Urbani,

Roberto Lande,a

Beatrice Di Carlo, and

Antonio Cassone

Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome, Italy

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)–γ. 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‐γ 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.

Received 31 December 2001; revised 13 March 2002; electronically published 17 July 2002.

Reprints or correspondence: Dr. Clara M. Ausiello, Dept. of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy ().

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  • Financial support: Istituto Superiore di Sanità, Ministry of Health, Italy (special projects Citochine come adiuvanti, Vaccini batterici, and Immunoterapici innovativi); Consiglio Nazionale delle Ricerche, Italy (special project Biotecnologie).

  • Present affiliation: Department of Immunology, Istituto Superiore di Sanità, Rome, Italy.

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