Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction

PLoS Pathogens

Nicola N. Lynskey¹  Shiranee Sriskandan¹  Mark Reglinski¹  Peter A. C. Wing¹  David Rigby²  Suneale Banerji²  Kayla A. Holder²  David G. Jackson²  Louise A. Johnson² 

[1] Faculty of Medicine, Imperial College London, London, United Kingdom;MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

关键词: Lymph nodes;    Bacterial pathogens;    Streptococcal infections;    Blood;    Mouse models;    Host-pathogen interactions;    Tropism;    Group A streptococcal infection;   

DOI  :  10.1371/journal.ppat.1005137

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY