CD4+ T cell immunity to Salmonella is transient in the circulation

While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccin...

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Autores principales:	Newton G. Peres, Nancy Wang, Paul Whitney, Sven Engel, Meghanashree M. Shreenivas, Ian Comerford, Dianna M. Hocking, Anna B. Erazo, Irmgard Förster, Andreas Kupz, Thomas Gebhardt, Shaun R. McColl, Stephen J. McSorley, Sammy Bedoui, Richard A. Strugnell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2cba44dd59ea4403844f41d34e30910e
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spelling	oai:doaj.org-article:2cba44dd59ea4403844f41d34e30910e2021-11-11T06:02:01ZCD4+ T cell immunity to Salmonella is transient in the circulation1553-73661553-7374https://doaj.org/article/2cba44dd59ea4403844f41d34e30910e2021-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568161/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently. Circulating Salmonella-reactive CD4+ T cells expressed the liver-homing chemokine receptor CXCR6, accumulated over time in the liver and assumed phenotypic characteristics associated with tissue-associated T cells. Liver memory CD4+ T cells showed TCR selection bias and their accumulation in the liver could be inhibited by blocking CXCL16. These data showed that the circulation of CD4+ T cells mediating immunity to Salmonella is limited to a brief window after which Salmonella-specific CD4+ T cells migrate to peripheral tissues. Our observations highlight the importance of triggering tissue-specific immunity against systemic infections. Author summary Helper T cells are essential for controlling infections by bacterial pathogens, such as Salmonella enterica var Typhimurium (S. Typhimurium). While it is well-established that this role is related to their provision of IFN-γ, when and where helper T cells elicit their protective function in vivo remains unresolved. We identified a protective helper T cell population in the circulation of mice early after inoculation with growth-attenuated S. Typhimurium strains; this population waned overtime. We observed that circulating helper T cell immunity can adoptively protect naïve recipient mice against lethal S. Typhimurium infection when harvested from a short time-window. In comparing helper T cell responses between spleen and liver in Salmonella-infected mice, we have observed a previously uncharacterized trafficking of helper T cells to the liver followed by the residence of S. Typhimurium-specific T cell memory in the organ. Taken together these findings identify that protective immunity to Salmonella infections is transient in the circulation and the liver as a preferential site of helper T memory cells.Newton G. PeresNancy WangPaul WhitneySven EngelMeghanashree M. ShreenivasIan ComerfordDianna M. HockingAnna B. ErazoIrmgard FörsterAndreas KupzThomas GebhardtShaun R. McCollStephen J. McSorleySammy BedouiRichard A. StrugnellPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Newton G. Peres Nancy Wang Paul Whitney Sven Engel Meghanashree M. Shreenivas Ian Comerford Dianna M. Hocking Anna B. Erazo Irmgard Förster Andreas Kupz Thomas Gebhardt Shaun R. McColl Stephen J. McSorley Sammy Bedoui Richard A. Strugnell CD4+ T cell immunity to Salmonella is transient in the circulation
description	While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently. Circulating Salmonella-reactive CD4+ T cells expressed the liver-homing chemokine receptor CXCR6, accumulated over time in the liver and assumed phenotypic characteristics associated with tissue-associated T cells. Liver memory CD4+ T cells showed TCR selection bias and their accumulation in the liver could be inhibited by blocking CXCL16. These data showed that the circulation of CD4+ T cells mediating immunity to Salmonella is limited to a brief window after which Salmonella-specific CD4+ T cells migrate to peripheral tissues. Our observations highlight the importance of triggering tissue-specific immunity against systemic infections. Author summary Helper T cells are essential for controlling infections by bacterial pathogens, such as Salmonella enterica var Typhimurium (S. Typhimurium). While it is well-established that this role is related to their provision of IFN-γ, when and where helper T cells elicit their protective function in vivo remains unresolved. We identified a protective helper T cell population in the circulation of mice early after inoculation with growth-attenuated S. Typhimurium strains; this population waned overtime. We observed that circulating helper T cell immunity can adoptively protect naïve recipient mice against lethal S. Typhimurium infection when harvested from a short time-window. In comparing helper T cell responses between spleen and liver in Salmonella-infected mice, we have observed a previously uncharacterized trafficking of helper T cells to the liver followed by the residence of S. Typhimurium-specific T cell memory in the organ. Taken together these findings identify that protective immunity to Salmonella infections is transient in the circulation and the liver as a preferential site of helper T memory cells.
format	article
author	Newton G. Peres Nancy Wang Paul Whitney Sven Engel Meghanashree M. Shreenivas Ian Comerford Dianna M. Hocking Anna B. Erazo Irmgard Förster Andreas Kupz Thomas Gebhardt Shaun R. McColl Stephen J. McSorley Sammy Bedoui Richard A. Strugnell
author_facet	Newton G. Peres Nancy Wang Paul Whitney Sven Engel Meghanashree M. Shreenivas Ian Comerford Dianna M. Hocking Anna B. Erazo Irmgard Förster Andreas Kupz Thomas Gebhardt Shaun R. McColl Stephen J. McSorley Sammy Bedoui Richard A. Strugnell
author_sort	Newton G. Peres
title	CD4+ T cell immunity to Salmonella is transient in the circulation
title_short	CD4+ T cell immunity to Salmonella is transient in the circulation
title_full	CD4+ T cell immunity to Salmonella is transient in the circulation
title_fullStr	CD4+ T cell immunity to Salmonella is transient in the circulation
title_full_unstemmed	CD4+ T cell immunity to Salmonella is transient in the circulation
title_sort	cd4+ t cell immunity to salmonella is transient in the circulation
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2cba44dd59ea4403844f41d34e30910e
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CD4+ T cell immunity to Salmonella is transient in the circulation

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