Siggins, M., Lynskey, N.N., Lamb, L.E. et al. (8 more authors) (Submitted: 2019) Lymphatic metastasis of virulent extracellular bacteria drives systemic infection. SSRN. (Submitted)
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 May 2019 09:29 |
Last Modified: | 30 May 2019 09:29 |
Status: | Submitted |
Publisher: | Elsevier |
Identification Number: | 10.2139/ssrn.3380255 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:146649 |