Abstract
Prior studies indicated that CD8+ T cells responding to a surrogate single antigen expressed by Y. pseudotuberculosis, ovalbumin, were insufficient to protect against yersiniosis. Herein we tested the hypothesis that CD8+ T cells reactive to the natural Yersinia antigen YopE would be more effective at providing mucosal protection. We first confirmed that immunization with the attenuated ksgA- strain of Y. pseudotuberculosis generated YopE-specific CD8+ T cells. These T cells were protective against challenge with virulent Listeria monocytogenes expressing secreted YopE. Mice immunized with an attenuated L. monocytogenes YopE+ strain generated large numbers of functional YopE-specific CD8+ T cells, and initially controlled a systemic challenge with virulent Y. pseudotuberculosis, yet eventually succumbed to yersiniosis. Mice vaccinated with a YopE peptide and cholera toxin vaccine generated robust T cell responses, providing protection to 60% of the mice challenged mucosally but failed to show complete protection against systemic infection with virulent Y. pseudotuberculosis. These studies demonstrate that vaccination with recombinant YopE vaccines can generate YopE-specific CD8+ T cells, that can provide significant mucosal protection but these cells are insufficient to provide sterilizing immunity against systemic Y. pseudotuberculosis infection. Our studies have implications for Yersinia vaccine development studies.
Highlights
Three Yersinia species cause disease in humans: Yersinia pestis, Yersinia enterocolitica and Yersinia pseudotuberculosis [1]
We show that mice immunization with Listeria monocytogenes expressing YopE or cholera toxin in addition to a YopE69-77 peptide resulted in the development of varying degrees of YopE-specific CD8+ T cell protection against Y. pseudotuberculosis systemic or mucosal infection
To determine if immunization with ksgAY. pseudotuberculosis stimulated YopE69-77-specific CD8+ T cells, we evaluated the frequency of Kb YopE69–77 tetramer-positive CD8+ T cells at day 8 post-intravenous inoculation with 200 CFU of ksgA- bacteria
Summary
Three Yersinia species cause disease in humans: Yersinia pestis, Yersinia enterocolitica and Yersinia pseudotuberculosis [1]. In the United States, Y. pestis infections occur mainly by inoculations from fleas carried by wild rodents [2], the last major plague outbreak in the US occurred in 1924 [3]. Ingestion of contaminated food or water is the source of enteric yersiniosis, caused by Y. enterocolitica or Y. pseudotuberculosis with swine being the most common source. This disease is characterized by fever, gastroenteritis and mesenteric lymphadenitis [4]. Albeit there are differences in routes of infection and disease severity, all Yersinia species are known to disseminate from lymphoid tissues to systemic organs. Many studies have demonstrated the ability of PLOS ONE | DOI:10.1371/journal.pone.0172314 February 16, 2017
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