title: Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.
abstract: 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.
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Felix R
authors.initials: FR
authors.lastname: Stahl
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Heller
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Halle
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Keyser
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Busche
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Marquardt
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Boelter
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bischoff
authors.affiliation: Helmholtz Zentrum München, Institut für Molekulare Immunologie, München, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Messerle
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017951:Antigen Presentation; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007422:Intestines / Q000276:immunology / Q000473:pathology / Q000821:virology; D008168:Lung / Q000254:growth & development / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000254:growth & development / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology*