Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction.
The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology.
Faculty of Medicine, Imperial College London, London, United Kingdom.
Nicola N
NN
Lynskey
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Suneale
S
Banerji
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Louise A
LA
Johnson
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Kayla A
KA
Holder
Faculty of Medicine, Imperial College London, London, United Kingdom.
Mark
M
Reglinski
Faculty of Medicine, Imperial College London, London, United Kingdom.
Peter A C
PA
Wing
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
David
D
Rigby
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
David G
DG
Jackson
Faculty of Medicine, Imperial College London, London, United Kingdom.
Shiranee
S
Sriskandan
D000818:Animals; D016470:Bacteremia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000276:immunology / Q000502:physiology*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007113:Immunity, Innate; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D042601:Lymphatic Vessels / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009154:Mutation; D011994:Recombinant Proteins / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000276:immunology / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D006023:Glycoproteins; D006820:Hyaluronic Acid; D026901:Membrane Transport Proteins; D011994:Recombinant Proteins; D033921:Vesicular Transport Proteins; C119248:LYVE1 protein, human; C492273:LYVE1 protein, mouse