puc-header

Lymphatic Metastasis of Virulent Extracellular Bacteria Drives Systemic Infection

42 Pages Posted: 19 May 2019 Sneak Peek Status: Review Complete

See all articles by Matthew Siggins

Matthew Siggins

Imperial College London - Department of Medicine; Imperial College London - MRC Centre for Molecular Bacteriology & Infection

Nicola N. Lynskey

Imperial College London - Department of Medicine; Imperial College London - MRC Centre for Molecular Bacteriology & Infection

Lucy E. Lamb

Imperial College London - Department of Medicine

Louise A. Johnson

University of Oxford - MRC Weatherall Institute of Molecular Medicine

Kristin K. Huse

Imperial College London - Department of Medicine; Imperial College London - MRC Centre for Molecular Bacteriology & Infection

Max Pearson

Imperial College London - Section of Infectious Diseases and Immunity; Imperial College London - Department of Medicine; Imperial College London - MRC Centre for Molecular Bacteriology & Infection

Suneale Banerji

University of Oxford - MRC Weatherall Institute of Molecular Medicine

Claire E. Turner

Imperial College London - Department of Medicine; University of Sheffield - Department of Molecular Biology and Biotechnology

Kevin Woollard

Imperial College London - Department of Medicine

David G. Jackson

University of Oxford - MRC Weatherall Institute of Molecular Medicine

Shiranee Sriskandan

Imperial College London - Department of Medicine; Imperial College London - MRC Centre for Molecular Bacteriology & Infection; Imperial College London - NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance

More...

Abstract

Lymphatic vessels carry fluid from tissues back to the bloodstream through filtering lymph nodes that limit infection and restrict passage of pathogens; ability to exploit these conduits is ascribed only to cancer cells and a small number of, principally intracellular, pathogens. Here, we report that Streptococcus pyogenes and other extracellular bacteria rapidly escape a local infection site and enter the blood circulation via the lymphatics, passing through sequential draining lymph nodes, and transiting in inter-nodal efferent lymphatic vessels, not blood vessels. Notably, S. pyogenes remain extracellular within lymphatic vessels and lymph nodes. By subverting innate immune responses to infection foci in lymph nodes, metastatic S. pyogenes replicate and seed intense bacteremia and systemic disease. Our findings identify extracellular lymphatic metastasis as the primary route of bacterial dissemination that provides both a survival niche and a conduit to reach the bloodstream and distant tissues for a range of bacteria.

Suggested Citation

Siggins, Matthew and Lynskey, Nicola N. and Lamb, Lucy E. and Johnson, Louise A. and Huse, Kristin K. and Pearson, Max and Banerji, Suneale and Turner, Claire E. and Woollard, Kevin and Jackson, David G. and Sriskandan, Shiranee, Lymphatic Metastasis of Virulent Extracellular Bacteria Drives Systemic Infection (April 30, 2019). Available at SSRN: https://ssrn.com/abstract=3380255 or http://dx.doi.org/10.2139/ssrn.3380255
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Matthew Siggins

Imperial College London - Department of Medicine ( email )

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Imperial College London - MRC Centre for Molecular Bacteriology & Infection ( email )

London
United Kingdom

Nicola N. Lynskey

Imperial College London - Department of Medicine

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Imperial College London - MRC Centre for Molecular Bacteriology & Infection

London
United Kingdom

Lucy E. Lamb

Imperial College London - Department of Medicine

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Louise A. Johnson

University of Oxford - MRC Weatherall Institute of Molecular Medicine

Oxford, Oxfordshire, England
United Kingdom

Kristin K. Huse

Imperial College London - Department of Medicine

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Imperial College London - MRC Centre for Molecular Bacteriology & Infection

London
United Kingdom

Max Pearson

Imperial College London - Section of Infectious Diseases and Immunity

London
United Kingdom

Imperial College London - Department of Medicine

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Imperial College London - MRC Centre for Molecular Bacteriology & Infection

London
United Kingdom

Suneale Banerji

University of Oxford - MRC Weatherall Institute of Molecular Medicine

Oxford, Oxfordshire, England
United Kingdom

Claire E. Turner

Imperial College London - Department of Medicine

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

University of Sheffield - Department of Molecular Biology and Biotechnology

United Kingdom

Kevin Woollard

Imperial College London - Department of Medicine

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

David G. Jackson

University of Oxford - MRC Weatherall Institute of Molecular Medicine

Oxford, Oxfordshire, England
United Kingdom

Shiranee Sriskandan (Contact Author)

Imperial College London - Department of Medicine ( email )

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Imperial College London - MRC Centre for Molecular Bacteriology & Infection ( email )

London
United Kingdom

Imperial College London - NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance ( email )

London
United Kingdom

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
148
Downloads
9