| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Immune Regulation Research Group, and
Adjuvant Research Group, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland
Whole cell pertussis vaccines (Pw) induce Th1 responses and protect against Bordetella pertussis infection, whereas pertussis acellular vaccines (Pa) induce Ab and Th2-biased responses and also protect against severe disease. In this study, we show that Pw failed to generate protective immunity in TLR4-defective C3H/HeJ mice. In contrast, protection induced with Pa was compromised, but not completely abrogated, in C3H/HeJ mice. Immunization with Pw, but not Pa, induced a population of IL-17-producing T cells (Th-17), as well as Th1 cells. Ag-specific IL-17 and IFN-
production was significantly lower in Pw-immunized TLR4-defective mice. Furthermore, treatment with neutralizing anti-IL-17 Ab immediately before and after B. pertussis challenge significantly reduced the protective efficacy of Pw. Stimulation of dendritic cells (DC) with Pw promoted IL-23, IL-12, IL-1
, and TNF-
production, which was impaired in DC from TLR4-defective mice. B. pertussis LPS, which is present in high concentrations in Pw, induced IL-23 production by DC, which enhanced IL-17 secretion by T cells, but the induction of Th-17 cells was also dependent on IL-1. In addition, we identified a new effector function for IL-17, activating macrophage killing of B. pertussis, and this bactericidal activity was less efficient in macrophages from TLR4-defective mice. These data provide the first definitive evidence of a role for TLRs in protective immunity induced by a human vaccine. Our findings also demonstrate that activation of innate immune cells through TLR4 helps to direct the induction of Th1 and Th-17 cells, which mediate protective cellular immunity to B. pertussis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a Science Foundation Ireland Principal Investigator Award (00/PI.I/B045; to K.H.G.M.).
2 Address correspondence and reprint requests to Dr. Kingston H. G. Mills, Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. E-mail address: kingston.mills{at}tcd.ie
3 Abbreviations used in this paper: Pw, whole cell pertussis vaccine; DC, dendritic cell; FHA, filamentous hemagglutinin; IL-1ra, IL-1R antagonist; LAL, Limulus amebocyte lysate; Pa, acellular pertussis vaccine; PT, pertussis toxin; Th-17, IL-17-producing T cell.
This article has been cited by other articles:
|
|
 |
|
  A. Freitas, J. C. Alves-Filho, T. Victoni, T. Secher, H. P. Lemos, F. Sonego, F. Q. Cunha, and B. Ryffel IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis J. Immunol., June 15, 2009; 182(12): 7846 - 7854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Minegishi, M. Saito, M. Nagasawa, H. Takada, T. Hara, S. Tsuchiya, K. Agematsu, M. Yamada, N. Kawamura, T. Ariga, et al. Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome J. Exp. Med., June 8, 2009; 206(6): 1291 - 1301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. McAleer, R. J. Rossi, and A. T. Vella Lipopolysaccharide Potentiates Effector T Cell Accumulation into Nonlymphoid Tissues through TRIF J. Immunol., May 1, 2009; 182(9): 5322 - 5330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Q. Zorzeto, H. G. Higashi, M. T. N. da Silva, E. d. F. Carniel, W. O. Dias, V. D. Ramalho, T. N. Mazzola, S. C. B. S. Lima, A. M. Morcillo, M. A. Stephano, et al. Immunogenicity of a Whole-Cell Pertussis Vaccine with Low Lipopolysaccharide Content in Infants Clin. Vaccine Immunol., April 1, 2009; 16(4): 544 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lombardi, L. Van Overtvelt, S. Horiot, and P. Moingeon Human Dendritic Cells Stimulated via TLR7 and/or TLR8 Induce the Sequential Production of Il-10, IFN-{gamma}, and IL-17A by Naive CD4+ T Cells J. Immunol., March 15, 2009; 182(6): 3372 - 3379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Stenger, M. C. M. Poelen, E. E. Moret, B. Kuipers, S. C. M. Bruijns, P. Hoogerhout, M. Hijnen, A. J. King, F. R. Mooi, C. J. P. Boog, et al. Immunodominance in Mouse and Human CD4+ T-Cell Responses Specific for the Bordetella pertussis Virulence Factor P.69 Pertactin Infect. Immun., February 1, 2009; 77(2): 896 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lim, S. C. Derrick, K. Kolibab, A. L. Yang, S. Porcelli, W. R. Jacobs, and S. L. Morris Early Pulmonary Cytokine and Chemokine Responses in Mice Immunized with Three Different Vaccines against Mycobacterium tuberculosis Determined by PCR Array Clin. Vaccine Immunol., January 1, 2009; 16(1): 122 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Rowan, J. M. Fletcher, E. J. Ryan, B. Moran, J. E. Hegarty, C. O'Farrelly, and K. H. G. Mills Hepatitis C Virus-Specific Th17 Cells Are Suppressed by Virus-Induced TGF-{beta} J. Immunol., October 1, 2008; 181(7): 4485 - 4494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Priebe, R. L. Walsh, T. A. Cederroth, A. Kamei, Y. S. Coutinho-Sledge, J. B. Goldberg, and G. B. Pier IL-17 Is a Critical Component of Vaccine-Induced Protection against Lung Infection by Lipopolysaccharide-Heterologous Strains of Pseudomonas aeruginosa J. Immunol., October 1, 2008; 181(7): 4965 - 4975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Jordan, M. E. Woods, J. Olano, and D. H. Walker The Absence of Toll-Like Receptor 4 Signaling in C3H/HeJ Mice Predisposes Them to Overwhelming Rickettsial Infection and Decreased Protective Th1 Responses Infect. Immun., August 1, 2008; 76(8): 3717 - 3724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. B. Hickey, C. F. Brereton, and K. H. G. Mills Adenylate cycalse toxin of Bordetella pertussis inhibits TLR-induced IRF-1 and IRF-8 activation and IL-12 production and enhances IL-10 through MAPK activation in dendritic cells J. Leukoc. Biol., July 1, 2008; 84(1): 234 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Fedele, M. Nasso, F. Spensieri, R. Palazzo, L. Frasca, M. Watanabe, and C. M. Ausiello Lipopolysaccharides from Bordetella pertussis and Bordetella parapertussis Differently Modulate Human Dendritic Cell Functions Resulting in Divergent Prevalence of Th17-Polarized Responses J. Immunol., July 1, 2008; 181(1): 208 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Cox, G. Shi, H. Yin, B. P. Vistica, E. F. Wawrousek, C.-C. Chan, and I. Gery Both Th1 and Th17 Are Immunopathogenic but Differ in Other Key Biological Activities J. Immunol., June 1, 2008; 180(11): 7414 - 7422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Fennelly, F. Sisti, S. C. Higgins, P. J. Ross, H. van der Heide, F. R. Mooi, A. Boyd, and K. H. G. Mills Bordetella pertussis Expresses a Functional Type III Secretion System That Subverts Protective Innate and Adaptive Immune Responses Infect. Immun., March 1, 2008; 76(3): 1257 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Scriba, B. Kalsdorf, D.-A. Abrahams, F. Isaacs, J. Hofmeister, G. Black, H. Y. Hassan, R. J. Wilkinson, G. Walzl, S. J. Gelderbloem, et al. Distinct, Specific IL-17- and IL-22-Producing CD4+ T Cell Subsets Contribute to the Human Anti-Mycobacterial Immune Response J. Immunol., February 1, 2008; 180(3): 1962 - 1970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Banus, R. W. B. Bottema, C. L. E. Siezen, R. J. Vandebriel, J. Reimerink, M. Mommers, G. H. Koppelman, B. Hoebee, C. Thijs, D. S. Postma, et al. Toll-Like Receptor 4 Polymorphism Associated with the Response to Whole-Cell Pertussis Vaccination in Children from the KOALA Study Clin. Vaccine Immunol., October 1, 2007; 14(10): 1377 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kryczek, S. Wei, L. Vatan, J. Escara-Wilke, W. Szeliga, E. T. Keller, and W. Zou Cutting Edge: Opposite Effects of IL-1 and IL-2 on the Regulation of IL-17+ T Cell Pool IL-1 Subverts IL-2-Mediated Suppression J. Immunol., August 1, 2007; 179(3): 1423 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Geurtsen, H. A. Banus, E. R. Gremmer, H. Ferguson, L. J. J. de la Fonteyne-Blankestijn, J. P. Vermeulen, J. A. M. A. Dormans, J. Tommassen, P. van der Ley, F. R. Mooi, et al. Lipopolysaccharide Analogs Improve Efficacy of Acellular Pertussis Vaccine and Reduce Type I Hypersensitivity in Mice Clin. Vaccine Immunol., July 1, 2007; 14(7): 821 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, O. M. Z. Howard, and J. J. Oppenheim Pertussis Toxin by Inducing IL-6 Promotes the Generation of IL-17-Producing CD4 Cells J. Immunol., May 15, 2007; 178(10): 6123 - 6129. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
