Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung
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Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung. / Stahl, Felix R; Heller, Katrin; Halle, Stephan; Keyser, Kirsten A; Busche, Andreas; Marquardt, Anja; Wagner, Karen; Boelter, Jasmin; Bischoff, Yvonne; Kremmer, Elisabeth; Arens, Ramon; Messerle, Martin; Förster, Reinhold.
in: PLOS PATHOG, Jahrgang 9, Nr. 12, 2013, S. e1003828.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung
AU - Stahl, Felix R
AU - Heller, Katrin
AU - Halle, Stephan
AU - Keyser, Kirsten A
AU - Busche, Andreas
AU - Marquardt, Anja
AU - Wagner, Karen
AU - Boelter, Jasmin
AU - Bischoff, Yvonne
AU - Kremmer, Elisabeth
AU - Arens, Ramon
AU - Messerle, Martin
AU - Förster, Reinhold
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Newborn
KW - Antigen Presentation
KW - Cells, Cultured
KW - Cytomegalovirus Infections
KW - Intestines
KW - Lung
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Muromegalovirus
KW - Pneumonia
KW - T-Lymphocytes
U2 - 10.1371/journal.ppat.1003828
DO - 10.1371/journal.ppat.1003828
M3 - SCORING: Journal article
C2 - 24348257
VL - 9
SP - e1003828
JO - PLOS PATHOG
JF - PLOS PATHOG
SN - 1553-7366
IS - 12
ER -