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

Nicola N. Lynskey, et al. 2015. PLoS Pathog 11(9): e1005137.

Speaker: Yi Tien (田 依)                                              Time: 13:00~14:00, Jan. 06, 2016

Commentator: Dr. Jenn-Wei Chen (陳振暐 教授)     Place: Room 601

Abstract

        Group A Streptococcus (GAS) is an important human pathogen and can cause severe invasive manifestations clinically. GAS possesses a wide variety of virulence factors, of which hyaluronan (HA) capsule consist in almost all serotypes. The defense factor of HA capsule not only against neutrophil-mediated opsonophagocytosis¹, but also may direct bacteria to disseminate in host. In previous study, GAS showed a particular ability to spread from infection site to adjacent draining lymph nodes. However, the basis of mechanism and subsequent pathogenesis for disease outcome are currently unknown. First, the author used wildtype M18 (hyper-encapsulated) and M89 (lower-encapsulated), and generated paired isogenic hyaluronan synthase mutant strains, to investigate whether the HA capsule can be a candidate to involve in this lymphatic tropism. In early infection, bacterial loads in draining lymph node were markedly lower in mice infected with M18_∆capsule and M89_∆capsule than in mice infected with wildtype strains. Lymphatic vessel endothelial receptor (LYVE)-1 is one of the HA binding receptors which is majorly expressed in lymph system². The LYVE-1 mediated encapsulated GAS adhesion in primary dermis endothelial cells from human (HDLEC) and murine (MDLEC), but do not interact with acapsular GAS. Furthermore, M18 were impeded to transit from local infection to lymph node in LYVE-1^-/- deficient mice. Similarly, LYVE-1 functional blockade in mice also limited M18 translocation to draining lymph nodes. Interestingly, bacteria burden were elevated in blood and spleen without LYVE-1 intervention. According to these findings, the authors revealed that GAS HA capsule-LYVE-1 interaction could lead rapid lymphatic dissemination but not via blood circulation. The lymphatic tropism of extracellular bacteria implicated the relevance in the pathogenesis of diverse disease spectrum in host.

References:

1.         Michael R. Wessels, et al, Proc. Nat. Acad. Sci. USA Vol. 88. (1999) Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci.

2.         Banerji S, et al, J Cell Biol 144:789–801. (1999) LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan.