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Dual actions of group B Streptococcus capsular sialic acid provide resistance to platelet-mediated antimicrobial killing.

Abstract：

:Circulating platelets have important functions in thrombosis and in modulating immune and inflammatory responses. However, the role of platelets in innate immunity to bacterial infection is largely unexplored. While human platelets rapidly kill Staphylococcus aureus, we found the neonatal pathogen group B Streptococcus (GBS) to be remarkably resistant to platelet killing. GBS possesses a capsule polysaccharide (CPS) with terminal α2,3-linked sialic acid (Sia) residues that mimic a common epitope present on the human cell surface glycocalyx. A GBS mutant deficient in CPS Sia was more efficiently killed by human platelets, thrombin-activated platelet releasate, and synthetic platelet-associated antimicrobial peptides. GBS Sia is known to bind inhibitory Sia-recognizing Ig superfamily lectins (Siglecs) to block neutrophil and macrophage activation. We show that human platelets also express high levels of inhibitory Siglec-9 on their surface, and that GBS can engage this receptor in a Sia-dependent manner to suppress platelet activation. In a mouse i.v. infection model, antibody-mediated platelet depletion increased susceptibility to platelet-sensitive S. aureus but did not alter susceptibility to platelet-resistant GBS. Elimination of murine inhibitory Siglec-E partially reversed platelet suppression in response to GBS infection. We conclude that GBS Sia has dual roles in counteracting platelet antimicrobial immunity: conferring intrinsic resistance to platelet-derived antimicrobial components and inhibiting platelet activation through engagement of inhibitory Siglecs. We report a bacterial virulence factor for evasion of platelet-mediated innate immunity.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Uchiyama S,Sun J,Fukahori K,Ando N,Wu M,Schwarz F,Siddiqui SS,Varki A,Marth JD,Nizet V

doi

10.1073/pnas.1815572116

subject

Has Abstract

pub_date

2019-04-09 00:00:00

pages

7465-7470

issue

eissn

0027-8424

issn

1091-6490

pii

1815572116

journal_volume

116

pub_type

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Dual actions of group B Streptococcus capsular sialic acid provide resistance to platelet-mediated antimicrobial killing.