Pneumococcal neuraminidases increase platelet killing by pneumolysin.

BACKGROUND

Platelets prevent extravasation of capillary fluids into the pulmonary interstitial tissue by sealing gaps in inflamed endothelium. This reduces respiratory distress associated with pneumonia. Streptococcus pneumoniae is the leading cause of severe community-acquired pneumonia. Pneumococci produce pneumolysin (PLY), which forms pores in membranes of eukaryotic cells including platelets. Additionally, pneumococci express neuraminidases, which cleave sialic acid residues from eukaryotic glycoproteins. In this study, we investigated the effect of desialylation on PLY binding and pore formation on platelets.

MATERIAL AND METHODS

We incubated human platelets with purified neuraminidases and PLY, nonencapsulated D39/TIGR4 and isogenic mutants deficient for PLY and/or NanA. We assessed platelet desialylation, PLY binding and pore formation by flow cytometry. We also analyzed the inhibitory potential of therapeutic immunoglobulin G preparations.

RESULTS

Pneumococci cause desialylation of platelet glycoproteins by neuraminidases, which is reduced by 90-100% in NanA-deficient mutants. NanC, cleaving only 2,3-linked sialic acid, induced platelet desialylation. PLY binding to platelets doubled (p=0.0166) and pore formation tripled (p=0.0373). A neuraminidase cleaving 2,3-, 2,6-, and 2,8-linked sialic acid like NanA was even more efficient. Addition of polyvalent IVIG decreased platelet desialylation induced by NanC up to 90% (p=0.263) and reduced pore formation >95% (p<0.0001) when incubated with pneumococci.

Informations de copyright

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Déclaration de conflit d'intérêts

The authors declare that they have no conflict of interest.