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

doi:10.1016/j.celrep.2016.12.038

Infection Programs Sustained Lymphoid Stromal Cell Responses and Shapes Lymph Node Remodeling upon Secondary Challenge

Cell Rep. 2017 Jan 10;18(2):406-418. doi: 10.1016/j.celrep.2016.12.038.

Authors

Affiliations

¹ Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
² 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.
³ Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
⁴ Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan.
⁵ Department of Organ Anatomy, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-8575, Japan.
⁶ 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.
⁷ 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: [email protected].

PMID: 28076785
DOI: 10.1016/j.celrep.2016.12.038

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.

Keywords: endothelial cells; fibroblastic reticular cells; immune response; lymph nodes; lymphocytes; lymphoid stromal cells; virus infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Viral / immunology
B-Lymphocytes / immunology
Cell Proliferation
Coinfection / immunology
Gene Expression Regulation
Kinetics
Lymph Nodes / pathology*
Mice, Inbred C57BL
Stromal Cells / pathology
Transcription, Genetic
Virus Diseases / genetics
Virus Diseases / immunology*
Virus Diseases / pathology*

Substances

Antigens, Viral