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Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7465-7470. doi: 10.1073/pnas.1815572116. Epub 2019 Mar 25.

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

Author information

1
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093; sauchiyama@ucsd.edu vnizet@ucsd.edu.
2
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093.
3
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093.
4
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
5
Department of Medicine, University of California, San Diego, La Jolla, CA 92093.
6
Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
7
Department of Biotechnology, American University of Ras Al Khaimah, 10021 Ras Al Khaima, United Arab Emirates.
8
Center for Nanomedicine, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037.
9
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106.

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.

KEYWORDS:

Siglec; group B Streptococcus; innate immunity; platelets; sialic acid

PMID:
30910970
PMCID:
PMC6462088
[Available on 2019-09-25]
DOI:
10.1073/pnas.1815572116
[Indexed for MEDLINE]

Conflict of interest statement

The authors declare no conflict of interest.

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