Dual actions of group B Streptococcus capsular sialic acid provide resistance to platelet-mediated antimicrobial killing
| Autor: | Shoib S. Siddiqui, Jamey D. Marth, Kyoko Fukahori, Ajit Varki, Josh Sun, Nao Ando, Satoshi Uchiyama, Flavio Schwarz, Mengyou Wu, Victor Nizet |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Multidisciplinary Innate immune system Antimicrobial peptides SIGLEC Microbiology Sialic acid 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Immune system chemistry Immunity 030220 oncology & carcinogenesis bacteria Platelet Platelet activation |
| Zdroj: | Proceedings of the National Academy of Sciences. 116:7465-7470 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1815572116 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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