The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
TLR4 Mediates Vaccine-Induced Protective Cellular Immunity to Bordetella pertussis : Role of IL-17-Producing T Cells
Abstract
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-γ 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-1β, and TNF-α 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.
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Cites
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“However, innate immune responses also direct adaptive immunity, in part through the production of cytokines, such as IL-12, which promote Th1 cell differentiation (31, 32).”
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IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
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Inferences, questions and possibilities in Toll-like receptor signalling
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Cited by
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
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Metadata
- Authors
- Higgins, S. C., Jarnicki, A. G., Lavelle, E. C., & Mills, K. H. G.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12-01
- Volume
- 177
- Issue
- 11
- Pages
- 7980-7989
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2149926345
- Cited by
- 353
- References
- 34
- FWCI
- 21.97
- Type
- journal article
- Language
- en
- Open access
- closed
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- Higgins, S. C., Jarnicki, A. G., Lavelle, E. C., & Mills, K. H. G. (2006). TLR4 Mediates Vaccine-Induced Protective Cellular Immunity to Bordetella pertussis : Role of IL-17-Producing T Cells. The Journal of Immunology. https://doi.org/10.4049/jimmunol.177.11.7980
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