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Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System

Francisella tularensis causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. The imm...

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Autores principales: Lindgren, Helena, Eneslätt, Kjell, Golovliov, Igor, Gelhaus, Carl, Rydén, Patrik, Wu, Terry, Sjöstedt, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280961/
https://www.ncbi.nlm.nih.gov/pubmed/32365846
http://dx.doi.org/10.3390/pathogens9050338
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author Lindgren, Helena
Eneslätt, Kjell
Golovliov, Igor
Gelhaus, Carl
Rydén, Patrik
Wu, Terry
Sjöstedt, Anders
author_facet Lindgren, Helena
Eneslätt, Kjell
Golovliov, Igor
Gelhaus, Carl
Rydén, Patrik
Wu, Terry
Sjöstedt, Anders
author_sort Lindgren, Helena
collection PubMed
description Francisella tularensis causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. The immune responses were characterized by use of splenocytes from naïve or Live vaccine strain- (LVS) or ∆clpB/∆wbtC-immunized Fischer 344 rats as effectors and bone marrow-derived macrophages infected with the highly virulent strain SCHU S4. A complex immune response was elicited, resulting in cytokine secretion, nitric oxide production, and efficient control of the intracellular bacterial growth. Addition of LVS-immune splenocytes elicited a significantly better control of bacterial growth than ∆clpB/∆wbtC splenocytes. This mirrored the efficacy of the vaccine candidates in the rat model. Lower levels of IFN-γ, TNF, fractalkine, IL-2, and nitrite were present in the co-cultures with ∆clpB/∆wbtC splenocytes than in those with splenocytes from LVS-immunized rats. Nitric oxide was found to be a correlate of protection, since the levels inversely correlated to the degree of protection and inhibition of nitric oxide production completely reversed the growth inhibition of SCHU S4. Overall, the results demonstrate that the co-culture assay with rat-derived cells is a suitable model to identify correlates of protection against highly virulent strains of F. tularensis
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spelling pubmed-72809612020-06-15 Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System Lindgren, Helena Eneslätt, Kjell Golovliov, Igor Gelhaus, Carl Rydén, Patrik Wu, Terry Sjöstedt, Anders Pathogens Article Francisella tularensis causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. The immune responses were characterized by use of splenocytes from naïve or Live vaccine strain- (LVS) or ∆clpB/∆wbtC-immunized Fischer 344 rats as effectors and bone marrow-derived macrophages infected with the highly virulent strain SCHU S4. A complex immune response was elicited, resulting in cytokine secretion, nitric oxide production, and efficient control of the intracellular bacterial growth. Addition of LVS-immune splenocytes elicited a significantly better control of bacterial growth than ∆clpB/∆wbtC splenocytes. This mirrored the efficacy of the vaccine candidates in the rat model. Lower levels of IFN-γ, TNF, fractalkine, IL-2, and nitrite were present in the co-cultures with ∆clpB/∆wbtC splenocytes than in those with splenocytes from LVS-immunized rats. Nitric oxide was found to be a correlate of protection, since the levels inversely correlated to the degree of protection and inhibition of nitric oxide production completely reversed the growth inhibition of SCHU S4. Overall, the results demonstrate that the co-culture assay with rat-derived cells is a suitable model to identify correlates of protection against highly virulent strains of F. tularensis MDPI 2020-04-30 /pmc/articles/PMC7280961/ /pubmed/32365846 http://dx.doi.org/10.3390/pathogens9050338 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lindgren, Helena
Eneslätt, Kjell
Golovliov, Igor
Gelhaus, Carl
Rydén, Patrik
Wu, Terry
Sjöstedt, Anders
Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System
title Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System
title_full Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System
title_fullStr Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System
title_full_unstemmed Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System
title_short Vaccine-Mediated Mechanisms Controlling Francisella tularensis SCHU S4 Growth in a Rat Co-Culture System
title_sort vaccine-mediated mechanisms controlling francisella tularensis schu s4 growth in a rat co-culture system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280961/
https://www.ncbi.nlm.nih.gov/pubmed/32365846
http://dx.doi.org/10.3390/pathogens9050338
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