PMID- 18498620 OWN - NLM STAT- MEDLINE DCOM- 20090318 LR - 20220330 IS - 1471-2172 (Electronic) IS - 1471-2172 (Linking) VI - 9 DP - 2008 May 22 TI - The role of Toll-like receptor-4 in pertussis vaccine-induced immunity. PG - 21 LID - 10.1186/1471-2172-9-21 [doi] AB - BACKGROUND: The gram-negative bacterium Bordetella pertussis is an important causative agent of pertussis, an infectious disease of the respiratory tract. After introduction of whole-cell vaccines (wP) in the 1950's, pertussis incidence has decreased significantly. Because wP were found to be reactogenic, in most developed countries they have been replaced by acellular vaccines (aP). We have previously shown a role for Toll-like receptor 4 (Tlr4) in pertussis-infected mice and the pertussis toxin (Ptx)-IgG response in wP-vaccinated children, raising the issue of the relative importance of Tlr4 in wP vaccination of mice. Here we analyze the effects of wP and aP vaccination and B. pertussis challenge, in Tlr4-deficient C3H/HeJ and wild-type C3H/HeOuJ mice. aP consists of Ptx, filamentous hemagglutinin (FHA), and pertactin (Prn). RESULTS: We show an important role of Tlr4 in wP and (to a lesser extent) aP vaccination, induction of Th1 and Th17 cells by wP but not aP vaccination, and induction of Th17 cells by infection, confirming data by Higgins et al. (J Immunol 2006, 177:7980-9). Furthermore, in Tlr4-deficient mice, compared to wild-type controls (i) after vaccination only, Ptx-IgG (that was induced by aP but not wP vaccination), FHA-IgG, and Prn-IgG levels were similar, (ii) after infection (only), lung IL-1alpha and IL-1beta expression were lower, (iii) after wP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while lung IL-1beta, TNF-alpha, IFN-gamma, IL-17, and IL-23 expression were lower, and lung pathology was absent, and (iv) after aP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while Ptx-IgG level was lower. CONCLUSION: Tlr4 does not influence the humoral response to vaccination (without challenge), plays an important role in natural immunity, wP and aP efficacy, and induction of Th1 and Th17 responses, is critical for lung pathology and enhances pro-inflammatory cytokine production after wP vaccination and challenge, and diminishes Th2 responses after both wP and aP vaccination and challenge. wP vaccination does not induce Ptx-IgG. A role for LPS in the efficacy of wP underlines the usefulness of LPS analogs to improve bacterial subunit vaccines such as aP. FAU - Banus, Sander AU - Banus S AD - Health Protection Research, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands. sander.banus@rivm.nl FAU - Stenger, Rachel M AU - Stenger RM FAU - Gremmer, Eric R AU - Gremmer ER FAU - Dormans, Jan A M A AU - Dormans JA FAU - Mooi, Frits R AU - Mooi FR FAU - Kimman, Tjeerd G AU - Kimman TG FAU - Vandebriel, Rob J AU - Vandebriel RJ LA - eng PT - Journal Article DEP - 20080522 PL - England TA - BMC Immunol JT - BMC immunology JID - 100966980 RN - 0 (Cytokines) RN - 0 (Pertussis Vaccine) RN - 0 (Toll-Like Receptor 4) RN - 0 (Vaccines, Acellular) SB - IM MH - Animals MH - Bordetella pertussis/*immunology MH - Cytokines/metabolism MH - Immunity, Active MH - Lymphocyte Activation/drug effects/immunology MH - Mice MH - Mice, Inbred C3H MH - Mice, Knockout MH - Pertussis Vaccine/*immunology/therapeutic use MH - Th1 Cells/immunology MH - Th2 Cells/immunology MH - Toll-Like Receptor 4/*immunology/*metabolism MH - Vaccination MH - Vaccines, Acellular/*immunology/therapeutic use MH - Whooping Cough/*immunology/pathology/*prevention & control PMC - PMC2409298 EDAT- 2008/05/24 09:00 MHDA- 2009/03/19 09:00 PMCR- 2008/05/22 CRDT- 2008/05/24 09:00 PHST- 2007/09/29 00:00 [received] PHST- 2008/05/22 00:00 [accepted] PHST- 2008/05/24 09:00 [pubmed] PHST- 2009/03/19 09:00 [medline] PHST- 2008/05/24 09:00 [entrez] PHST- 2008/05/22 00:00 [pmc-release] AID - 1471-2172-9-21 [pii] AID - 10.1186/1471-2172-9-21 [doi] PST - epublish SO - BMC Immunol. 2008 May 22;9:21. doi: 10.1186/1471-2172-9-21.