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Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
PLoS Pathog. 9:e1003828 (2013)
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
ISSN (print) / ISBN
1553-7366
e-ISSN
1553-7374
Zeitschrift
PLoS Pathogens
Quellenangaben
Band: 9,
Heft: 12,
Artikelnummer: e1003828
Verlag
Public Library of Science (PLoS)
Verlagsort
San Francisco
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Immunology (IMI)