title: Local CD11c+ MHC class II- precursors generate lung dendritic cells during respiratory viral infection, but are depleted in the process.
abstract: Increases in numbers of lung dendritic cells (DC) observed during respiratory viral infections are assumed to be due to recruitment from bone marrow precursors. No local production has been demonstrated. In this study, we isolated defined populations of murine lung cells based on CD11c and MHC class II (MHC II) expression. After culture for 12 days with GM-CSF, we analyzed cell numbers, DC surface markers, and Ag-presenting capacity. Only CD11c+ MHC II- cells from naive mice proliferated, yielding myeloid DC, which induced Ag-specific proliferation of naive T cells. After respiratory syncytial virus (RSV) infection, numbers of pulmonary CD11c+ MHC II- precursor cells were significantly reduced and DC could not be generated. Moreover, RSV infection prevented subsequent in vivo expansion of pulmonary DC in response to influenza infection or LPS treatment. These results provide direct evidence of local generation of fully functional myeloid DC in the lung from CD11c+ MHC II(-) precursor cells that are depleted by RSV infection, leading to an inability to expand lung DC numbers in response to subsequent viral infection or exposure to bacterial products. This depletion of local DC precursors in respiratory viral infections may be important in explaining complex interactions between multiple and intercurrent pulmonary infections.
authors.affiliation: Department of Respiratory Medicine, National Heart and Lung Institute and Wright Fleming Institute of Infection and Immunity, Imperial College London, Norfolk Place, London, United Kingdom.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Nina
authors.initials: N
authors.lastname: Peters
authors.forename: Vasile
authors.initials: V
authors.lastname: Laza-Stanca
authors.forename: Niga
authors.initials: N
authors.lastname: Nawroly
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schwarze
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance; D009980:Influenza A virus / Q000276:immunology; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology; D011024:Pneumonia, Viral / Q000276:immunology* / Q000473:pathology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000473:pathology
chemical_list: D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II