title: Salivary gland resident APCs are Flt3L- and CCR2-independent macrophage-like cells incapable of cross-presentation.
abstract: Cytomegaloviruses (CMVs) disseminate within the human population via mucosal excretions, for example, from the salivary glands (SGs), which represent a privileged site of viral immune evasion and persistence. The murine CMV (MCMV) model has served to identify factors that maintain a unique virus-host relationship in this organ. In contrast to all other organs, the SG is resistant to CD8(+) T-cell mediated control of MCMV replication due to virally induced MHC class I downregulation, which is exceptionally efficient in acinar glandular epithelial cells. Uniquely to the SG, IFN-γ producing CD4(+) T cells are required for virus control. While T-cell responses have been extensively characterized in the SG, the ontogeny and function of APCs in this organ remain to be assessed. Here, we show that macrophage-like cells constitute the population of SG-resident APCs in steady state and during MCMV-induced inflammation in mice. Inflammatory monocytes, monocyte-derived DCs as well as conventional, Flt3L-dependent DCs do not contribute to this population. Despite supporting contact formation to CD4(+) and CD8(+) T cells in principle, SG-resident APCs fail to activate the latter due to their inability to cross-present MCMV-derived antigen.
authors.affiliation: Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Thom
authors.forename: Senta M
authors.initials: SM
authors.lastname: Walton
authors.forename: Nicole
authors.initials: N
authors.lastname: Torti
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D010641:Phenotype; D054390:Receptors, CCR2 / Q000378:metabolism*; D012469:Salivary Glands / Q000276:immunology* / Q000821:virology
chemical_list: D000956:Antigens, Viral; D015415:Biomarkers; D008565:Membrane Proteins; D054390:Receptors, CCR2; C084881:flt3 ligand protein
keywords: APCs; cross-presentation; cytomegalovirus; epithelial immunity; persistent virus infection