Nodular Inflammatory Foci Are Sites of T Cell Priming and Control of Murine Cytomegalovirus Infection in the Neonatal Lung: e1003828

• Published in: PLoS pathogens 2013-12, Vol.9 (12)
• 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, ster, Reinhold
• Format: Article
• Language: English
• Subjects: Cytomegalovirus; Immune system; Infections; Murine cytomegalovirus; Rodents
• ISSN: 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.