title: IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis infection.
abstract: Pneumonic plague is one of the world's most deadly infectious diseases. The causative bacterium, Yersinia pestis, has the potential to be exploited as a biological weapon, and no vaccine is available. Vaccinating B cell-deficient mice with D27-pLpxL, a live attenuated Y. pestis strain, induces cell-mediated protection against lethal pulmonary Y. pestis challenge. In this article, we demonstrate that prime/boost vaccination with D27-pLpxL confers better protection than prime-only vaccination. The improved survival does not result from enhanced bacterial clearance but is associated with increased levels of IL-17 mRNA and protein in the lungs of challenged mice. The boost also increases pulmonary numbers of IL-17-producing CD4 T cells. Interestingly, most of these cells simultaneously produce canonical type 1 and type 17 cytokines; most produce IL-17 and TNF-α, and many produce IL-17, TNF-α, and IFN-γ. Neutralizing IL-17 counteracts the improved survival associated with prime/boost vaccination without significantly impacting bacterial burden. Thus, IL-17 appears to mediate the enhanced protection conferred by booster immunization. Although neutralizing IL-17 significantly reduces neutrophil recruitment to the lungs of mice challenged with Y. pestis, this impact is equally evident in mice that receive one or two immunizations with D27-pLpxL, suggesting it cannot suffice to account for the improved survival that results from booster immunization. We conclude that IL-17 plays a yet to be identified role in host defense that enhances protection against pulmonary Y. pestis challenge, and we suggest that pneumonic plague vaccines should aim to induce mixed type 1 and type 17 cellular responses.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA.
authors.forename: Jr-Shiuan
authors.initials: JS
authors.lastname: Lin
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Kummer
authors.forename: Frank M
authors.initials: FM
authors.lastname: Szaba
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smiley
mesh_terms: D000217:Acyltransferases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods; D020381:Interleukin-17 / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010930:Plague / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D029968:Escherichia coli Proteins; C098680:Il17a protein, mouse; D020381:Interleukin-17; D010931:Plague Vaccine; D019444:Vaccines, DNA; D000217:Acyltransferases; C492237:LpxL protein, E coli