Lymphatic Vessels Balance Viral Dissemination and Immune Activation following Cutaneous Viral Infection

Christopher P. Loo, Nicholas A. Nelson, Ryan S. Lane, Jamie L. Booth, Sofia C. Loprinzi Hardin, Archana Thomas, Mark Slifka, Jeffrey Nolz, Amanda Lund

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Lymphatic vessels lie at the interface between peripheral sites of pathogen entry, adaptive immunity, and the systemic host. Though the paradigm is that their open structure allows for passive flow of infectious particles from peripheral tissues to lymphoid organs, virus applied to skin by scarification does not spread to draining lymph nodes. Using cutaneous infection by scarification, we analyzed the effect of viral infection on lymphatic transport and evaluated its role at the host-pathogen interface. We found that, in the absence of lymphatic vessels, canonical lymph-node-dependent immune induction was impaired, resulting in exacerbated pathology and compensatory, systemic priming. Furthermore, lymphatic vessels decouple fluid and cellular transport in an interferon-dependent manner, leading to viral sequestration while maintaining dendritic cell transport for immune induction. In conclusion, we found that lymphatic vessels balance immune activation and viral dissemination and act as an “innate-like” component of tissue host viral defense. Loo et al. challenge the prevailing view that lymphatic vessels are passive conduits that flush antigen and pathogens to lymphoid tissue. Rather, the authors demonstrate that lymphatic vessels are a selective and active barrier that efficiently coordinates immune activation while also limiting viral spread and subsequent immune pathology.

Original languageEnglish (US)
Pages (from-to)3176-3187
Number of pages12
JournalCell Reports
Volume20
Issue number13
DOIs
StatePublished - Sep 26 2017

Keywords

  • cutaneous infection
  • dissemination
  • lymphatic vessels
  • tissue immunity
  • tissue microenvironment
  • type I interferons
  • vaccinia virus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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