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* Department of Infectious, Parasitic and Immune-mediated Diseases, Anti-infectious Immunity Unit, Istituto Superiore di Sanità, Rome, Italy; and
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH 45267-0524
Bordetella pertussis and B. parapertussis are the etiological agents of pertussis, yet the former has a higher incidence and is the cause of a more severe disease, in part due to pertussis toxin. To identify other factors contributing to the different pathogenicity of the two species, we analyzed the capacity of structurally different lipooligosaccharide (LOS) from B. pertussis and LPS from B. parapertussis to influence immune functions regulated by dendritic cells. Either B. pertussis LOS and B. parapertussis LPS triggered TLR4 signaling and induced phenotypic maturation and IL-10, IL-12p40, IL-23, IL-6, and IL-1β production in human monocyte-derived dendritic cells (MDDC). B. parapertussis LPS was a stronger inducer of all these activities as compared with B. pertussis LOS, with the notable exception of IL-1β, which was equally produced. Only B. parapertussis LPS was able to induce IL-27 expression. In addition, although MDDC activation induced by B. parapertussis LPS was greatly dependent on soluble CD14, B. pertussis LOS activity was CD14-independent. The analysis of the intracellular pathways showed that B. parapertussis LPS and B. pertussis LOS equally induced I
B
and p38 MAPK phosphorylation, but B. pertussis LOS triggered ERK1/2 phosphorylation more rapidly and at higher levels than B. parapertussis LPS. Furthermore, B. pertussis LOS was unable to induce MyD88-independent gene induction, which was instead activated by B. parapertussis LPS, witnessed by STAT1 phosphorylation and induction of the IFN-dependent genes, IFN regulatory factor-1 and IFN-inducible protein-10. These differences resulted in a divergent regulation of Th cell responses, B. pertussis LOS MDDC driving a predominant Th17 polarization. Overall, the data observed reflect the different structure of the two LPS and the higher Th17 response induced by B. pertussis LOS may contribute to the severity of pertussis in humans.
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1 This work was supported by Grants 5303 and 28C6 from Istituto Superiore di Sanità-National Institutes of Health (USA) Scientific Cooperation Agreement, by Grant 6ACF/6 from the Italian Ministry of Health, Istituto Superiore di Sanità, Sixth AIDS Project and l’Agenzia Italiana del Farmaco Project (to C.M.A.), and Contract LSHP-CT-2003-503240 from the Commission of the European Communities, Sixth Framework Program, "Mucosal Vaccines for Poverty-Related Diseases."
2 Current address: Graduate School of Infection Control Sciences, Kitasato University 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
3 Address correspondence and reprint requests to Dr. Clara M. Ausiello, Department of Infectious, Parasitic and Immune-mediated Diseases, Anti-infectious Immunity Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. E-mail address: clara.ausiello{at}iss.it
4 Abbreviations used in this paper: LOS, lipooligosaccharide; IP, IFN-inducible protein; IRF, IFN regulatory factor; HEK, human epithelial kidney; EBI, EBV-induced gene; DC, dendritic cell; MDDC, monocyte-derived DC; SEAP, secreted alkaline phosphatase.
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  C. Andreasen and N. H. Carbonetti Pertussis Toxin Inhibits Early Chemokine Production To Delay Neutrophil Recruitment in Response to Bordetella pertussis Respiratory Tract Infection in Mice Infect. Immun., November 1, 2008; 76(11): 5139 - 5148. [Abstract] [Full Text] [PDF]
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