title: Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge.
abstract: Lymph nodes (LNs) are constructed of intricate networks of endothelial and mesenchymal stromal cells. How these lymphoid stromal cells (LSCs) regulate lymphoid tissue remodeling and contribute to immune responses remains poorly understood. We performed a comprehensive functional and transcriptional analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly, with different kinetics for distinct pathogens. Recruitment of cells to inflamed LNs induced LSC expansion, while B cells sustained stromal responses in an antigen-independent manner. Infection induced rapid transcriptional responses in LSCs. This transcriptional program was transient, returning to homeostasis within 1 month of infection, yet expanded fibroblastic reticular cell networks persisted for more than 3 months after infection, and this altered LN composition reduced the magnitude of LSC responses to subsequent heterologous infection. Our results reveal the complexity of LSC responses during infection and suggest that amplified networks of LN stromal cells support successive immune responses.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Gregory
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Walter
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
authors.forename: Yannick O
authors.initials: YO
authors.lastname: Alexandre
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, VIC 3000, Australia.
authors.forename: Jyh Liang
authors.initials: JL
authors.lastname: Hor
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
authors.forename: Joel Z
authors.initials: JZ
authors.lastname: Ma
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, VIC 3000, Australia.
authors.forename: Sapna
authors.initials: S
authors.lastname: Devi
authors.affiliation: Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Tokuda
authors.affiliation: Department of Organ Anatomy, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-8575, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Mackay
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Mathematics and Statistics, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, VIC 3000, Australia.
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, VIC 3000, Australia. Electronic address: smue@unimelb.edu.au.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D060085:Coinfection / Q000276:immunology; D005786:Gene Expression Regulation; D007700:Kinetics; D008198:Lymph Nodes / Q000473:pathology*; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000473:pathology; D014158:Transcription, Genetic; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
chemical_list: D000956:Antigens, Viral
keywords: endothelial cells; fibroblastic reticular cells; immune response; lymph nodes; lymphocytes; lymphoid stromal cells; virus infection