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Updated: Jun 5, 2026
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis infection
Jr-Shiuan Lin1, Lawrence W Kummer, Frank M Szaba
1Trudeau Institute, Saranac Lake, NY 12983, USA.
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.
Insights
Prime/boost vaccination with a live attenuated Yersinia pestis strain enhances survival against pneumonic plague. This improved protection is mediated by Interleukin-17 (IL-17) and mixed cellular responses.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Pneumonic plague, caused by Yersinia pestis, is a highly lethal disease with no available vaccine.
- Yersinia pestis poses a potential bioterrorism threat.
- Current research focuses on developing effective prophylactic measures against Y. pestis infection.
Purpose of the Study:
- To evaluate the efficacy of prime/boost vaccination with a live attenuated Yersinia pestis strain (D27-pLpxL) in a mouse model.
- To elucidate the immunological mechanisms underlying enhanced protection conferred by booster immunization.
- To investigate the role of Interleukin-17 (IL-17) in vaccine-induced protection against pneumonic plague.
Main Methods:
- B cell-deficient mice were vaccinated with D27-pLpxL (attenuated Y. pestis strain).
- Vaccination strategies included prime-only and prime/boost regimens.
- Immune responses were assessed by measuring bacterial burden, cytokine levels (IL-17, TNF-α, IFN-γ), and immune cell populations (CD4 T cells) in the lungs.
- Neutralizing antibodies against IL-17 were used to determine its role in protection.
Main Results:
- Prime/boost vaccination significantly improved survival compared to prime-only vaccination against lethal Y. pestis challenge.
- Enhanced survival was associated with increased IL-17 mRNA and protein levels in the lungs.
- Booster immunization increased the number of IL-17-producing CD4 T cells, many co-producing TNF-α and IFN-γ.
- Neutralization of IL-17 partially abrogated the survival benefit of prime/boost vaccination, without affecting bacterial clearance.
Conclusions:
- Prime/boost vaccination with D27-pLpxL confers enhanced protection against pneumonic plague, mediated by IL-17.
- IL-17 plays a crucial role in host defense against Y. pestis, independent of bacterial clearance.
- Future pneumonic plague vaccines should aim to induce mixed type 1 and type 17 cellular immune responses for optimal efficacy.
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