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

• Published in: PLoS pathogens Vol. 9; no. 12; p. e1003828
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2013; Public Library of Science (PLoS)
• Subjects: Animals; Animals, Newborn; Antigen Presentation; Cell research; Cells, Cultured; Cytomegalovirus; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - pathology; Cytomegalovirus Infections - virology; Cytomegaloviruses; Health aspects; Host-parasite relationships; Immune system; Infections; Intestines - immunology; Intestines - pathology; Intestines - virology; Lung - growth & development; Lung - immunology; Lung - pathology; Lung - virology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muromegalovirus - growth & development; Muromegalovirus - immunology; Physiological aspects; Pneumonia - immunology; Pneumonia - pathology; Pneumonia - virology; Rodents; T cells; T-Lymphocytes - immunology; Netherlands; Animals, Newborn; Intestines; Pneumonia; T-Lymphocytes; Lymphocyte Activation; Lung; Mice, Inbred C57BL; Cells, Cultured; Cytomegalovirus Infections; Muromegalovirus; Mice, Transgenic; Animals; Antigen Presentation; Mice
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003828

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.