Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.

Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements...

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Autores principales:	Deborah D Crane, Dana P Scott, Catharine M Bosio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1553e321cd88411db626d4f2b11ff2cd
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spelling	oai:doaj.org-article:1553e321cd88411db626d4f2b11ff2cd2021-11-18T07:25:24ZGeneration of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.1932-620310.1371/journal.pone.0033349https://doaj.org/article/1553e321cd88411db626d4f2b11ff2cd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22428026/?tool=EBIhttps://doaj.org/toc/1932-6203Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR(+) cells, γδTCR(+) cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4(+) and CD8(+) cells are the primary producers of IFN-γand that γδTCR(+) cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection.Deborah D CraneDana P ScottCatharine M BosioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33349 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Deborah D Crane Dana P Scott Catharine M Bosio Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.
description	Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR(+) cells, γδTCR(+) cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4(+) and CD8(+) cells are the primary producers of IFN-γand that γδTCR(+) cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection.
format	article
author	Deborah D Crane Dana P Scott Catharine M Bosio
author_facet	Deborah D Crane Dana P Scott Catharine M Bosio
author_sort	Deborah D Crane
title	Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.
title_short	Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.
title_full	Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.
title_fullStr	Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.
title_full_unstemmed	Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.
title_sort	generation of a convalescent model of virulent francisella tularensis infection for assessment of host requirements for survival of tularemia.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1553e321cd88411db626d4f2b11ff2cd
work_keys_str_mv	AT deborahdcrane generationofaconvalescentmodelofvirulentfrancisellatularensisinfectionforassessmentofhostrequirementsforsurvivaloftularemia AT danapscott generationofaconvalescentmodelofvirulentfrancisellatularensisinfectionforassessmentofhostrequirementsforsurvivaloftularemia AT catharinembosio generationofaconvalescentmodelofvirulentfrancisellatularensisinfectionforassessmentofhostrequirementsforsurvivaloftularemia
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Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.

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