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.


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*


  • Antigens, Viral