title: Measles virus infection of alveolar macrophages and dendritic cells precedes spread to lymphatic organs in transgenic mice expressing human signaling lymphocytic activation molecule (SLAM, CD150).
abstract: Recent studies of primate models suggest that wild-type measles virus (MV) infects immune cells located in the airways before spreading systemically, but the identity of these cells is unknown. To identify cells supporting primary MV infection, we took advantage of mice expressing the MV receptor human signaling lymphocyte activation molecule (SLAM, CD150) with human-like tissue specificity. We infected these mice intranasally (IN) with a wild-type MV expressing green fluorescent protein. One, two, or three days after inoculation, nasal-associated lymphoid tissue (NALT), the lungs, several lymph nodes (LNs), the spleen, and the thymus were collected and analyzed by microscopy and flow cytometry, and virus isolation was attempted. One day after inoculation, MV replication was documented only in the airways, in about 2.5% of alveolar macrophages (AM) and 0.5% of dendritic cells (DC). These cells expressed human SLAM, and it was observed that MV infection temporarily enhanced SLAM expression. Later, MV infected other immune cell types, including B and T lymphocytes. Virus was isolated from lymphatic tissue as early as 2 days post-IN inoculation; the mediastinal lymph node was an early site of replication and supported high levels of infection. Three days after intraperitoneal inoculation, 1 to 8% of the mediastinal LN cells were infected. Thus, MV infection of alveolar macrophages and subepithelial dendritic cells in the airways precedes infection of lymphocytes in lymphatic organs of mice expressing human SLAM with human-like tissue specificity.
authors.affiliation: Department of Molecular Medicine, and Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Claudia S Antunes
authors.initials: CS
authors.lastname: Ferreira
authors.forename: Marie
authors.initials: M
authors.lastname: Frenzke
authors.forename: Vincent H J
authors.initials: VH
authors.lastname: Leonard
authors.forename: G Grant
authors.initials: GG
authors.lastname: Welstead
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Richardson
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000821:virology; D008221:Lymphoid Tissue / Q000378:metabolism / Q000821:virology*; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000821:virology*; D008457:Measles / Q000276:immunology* / Q000473:pathology; D008459:Measles virus / Q000378:metabolism* / Q000472:pathogenicity; D051379:Mice; D008822:Mice, Transgenic; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; C508032:Ifnar1 protein, mouse; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D053633:Receptor, Interferon alpha-beta; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1