IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis infection

J Immunol. 2011 Feb 1;186(3):1675-84. doi: 10.4049/jimmunol.1003303. Epub 2010 Dec 20.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyltransferases / administration & dosage
  • Acyltransferases / genetics
  • Acyltransferases / immunology
  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / genetics
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Dose-Response Relationship, Immunologic
  • Escherichia coli Proteins / administration & dosage
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology
  • Immunity, Cellular* / genetics
  • Immunization Schedule
  • Immunization, Secondary / methods
  • Interleukin-17 / administration & dosage
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / physiology*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Plague / immunology*
  • Plague / mortality
  • Plague / prevention & control*
  • Plague Vaccine / administration & dosage*
  • Plague Vaccine / genetics
  • Plague Vaccine / immunology*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology
  • Yersinia pestis / genetics
  • Yersinia pestis / immunology*

Substances

  • Adjuvants, Immunologic
  • Escherichia coli Proteins
  • Il17a protein, mouse
  • Interleukin-17
  • Plague Vaccine
  • Vaccines, DNA
  • Acyltransferases
  • LpxL protein, E coli