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Stahl, F.R.* ; Heller, K.* ; Halle, S.* ; Keyser, K.A.* ; Busche, A.* ; Marquardt, A.* ; Wagner, K.* ; Boelter, J.* ; Bischoff, Y.* ; Kremmer, E. ; Arens, R.* ; Messerle, M.* ; Forster, R.*

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

PLoS Pathog. 9:e1003828 (2013)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Subcapsular Sinus Macrophages; Natural-killer-cells; Class-i Complexes; Mouse Cytomegalovirus; Interstitial Pneumonia; Immune Evasion; Virus; Mice; Pathogenesis; Model
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Zeitschrift PLoS Pathogens
Quellenangaben Band: 9, Heft: 12, Seiten: , Artikelnummer: e1003828 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort San Francisco
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501793-001
PubMed ID 24348257
DOI 10.1371/journal.ppat.1003828
WOS ID WOS:000330535400055
Scopus ID 84892862217
Erfassungsdatum 2013-12-31
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