Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV) infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mut...

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Autores principales: Felix R Stahl, Katrin Heller, Stephan Halle, Kirsten A Keyser, Andreas Busche, Anja Marquardt, Karen Wagner, Jasmin Boelter, Yvonne Bischoff, Elisabeth Kremmer, Ramon Arens, Martin Messerle, Reinhold Förster
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spelling oai:doaj.org-article:1b6b9c02372e45b19a3729b5c0d6b8e12021-11-18T06:07:14ZNodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.1553-73661553-737410.1371/journal.ppat.1003828https://doaj.org/article/1b6b9c02372e45b19a3729b5c0d6b8e12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24348257/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV) infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV) we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+) T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF) in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC) interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.Felix R StahlKatrin HellerStephan HalleKirsten A KeyserAndreas BuscheAnja MarquardtKaren WagnerJasmin BoelterYvonne BischoffElisabeth KremmerRamon ArensMartin MesserleReinhold FörsterPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 12, p e1003828 (2013)
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
Felix R Stahl
Katrin Heller
Stephan Halle
Kirsten A Keyser
Andreas Busche
Anja Marquardt
Karen Wagner
Jasmin Boelter
Yvonne Bischoff
Elisabeth Kremmer
Ramon Arens
Martin Messerle
Reinhold Förster
Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
description Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV) infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV) we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+) T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF) in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC) interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.
format article
author Felix R Stahl
Katrin Heller
Stephan Halle
Kirsten A Keyser
Andreas Busche
Anja Marquardt
Karen Wagner
Jasmin Boelter
Yvonne Bischoff
Elisabeth Kremmer
Ramon Arens
Martin Messerle
Reinhold Förster
author_facet Felix R Stahl
Katrin Heller
Stephan Halle
Kirsten A Keyser
Andreas Busche
Anja Marquardt
Karen Wagner
Jasmin Boelter
Yvonne Bischoff
Elisabeth Kremmer
Ramon Arens
Martin Messerle
Reinhold Förster
author_sort Felix R Stahl
title Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
title_short Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
title_full Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
title_fullStr Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
title_full_unstemmed Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
title_sort nodular inflammatory foci are sites of t cell priming and control of murine cytomegalovirus infection in the neonatal lung.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/1b6b9c02372e45b19a3729b5c0d6b8e1
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