Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge
Julia L. Gregory,
Anne Walter,
Yannick O. Alexandre,
Jyh Liang Hor,
Ruijie Liu,
Joel Z. Ma,
Sapna Devi,
Nobuko Tokuda,
Yuji Owada,
Laura K. Mackay,
Gordon K. Smyth,
William R. Heath,
Scott N. Mueller
Affiliations
Julia L. Gregory
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Anne Walter
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Yannick O. Alexandre
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Jyh Liang Hor
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
Ruijie Liu
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia
Joel Z. Ma
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Sapna Devi
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
Nobuko Tokuda
Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan
Yuji Owada
Department of Organ Anatomy, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-8575, Japan
Laura K. Mackay
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia
Gordon K. Smyth
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
William R. Heath
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
Scott N. Mueller
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; Corresponding author
Summary: 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. : Lymph nodes are constructed of intricate networks of stromal cells. Gregory et al. reveal a robust yet transient transcriptional program in lymph node stromal cells induced by virus infection. Previously primed lymph nodes sustained amplified networks of stromal cells that supported subsequent immune responses. Keywords: lymphoid stromal cells, fibroblastic reticular cells, endothelial cells, lymph nodes, immune response, virus infection, lymphocytes
