J Immunol. 2016 Mar 30. pii: 1502709. [Epub ahead of print]

Pneumococcal Surface Protein A Plays a Major Role in Streptococcus pneumoniae-Induced Immunosuppression.

Saumyaa1, Pujanauski L2, Colino J3, Flora M4, Torres RM2, Tuomanen E5, Snapper CM6.

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Intact, inactivatedStreptococcus pneumoniae[including the unencapsulatedS. pneumoniae,serotype 2 strain (R36A)] markedly inhibits the humoral immune response to coimmunized heterologous proteins, a property not observed with several other intact Gram-positive or Gram-negative bacteria. In this study, we determined the nature of this immunosuppressive property. Because phosphorylcholine (PC), a major haptenic component of teichoic acid in theS. pneumoniaecell wall, and lipoteichoic acid in theS. pneumoniaemembrane were previously reported to be immunosuppressive when derived from filarial parasites, we determined whether R36A lacking PC (R36Apc-) was inhibitory. Indeed, although R36Apc-exhibited a markedly reduced level of inhibition of the IgG response to coimmunized chicken OVA (cOVA), no inhibition was observed when using several other distinct PC-expressing bacteria or a soluble, protein-PC conjugate. Further, treatment of R36A with periodate, which selectively destroys PC residues, had no effect on R36A-mediated inhibition. Because R36Apc-also lacks choline-binding proteins (CBPs) that require PC for cell wall attachment, and because treatment of R36A with trypsin eliminated its inhibitory activity, we incubated R36A in choline chloride, which selectively strips CBPs from its surface. R36A lacking CBPs lost most of its inhibitory property, whereas the supernatant of choline chloride-treated R36A, containing CBPs, was markedly inhibitory. Coimmunization studies using cOVA and variousS. pneumoniaemutants, each genetically deficient in one of the CBPs, demonstrated that onlyS. pneumoniaelacking the CBP pneumococcal surface protein A lost its ability to inhibit the IgG anti-cOVA response. These results strongly suggest that PspA plays a major role in mediating the immunosuppressive property ofS. pneumoniae.

Copyright © 2016 by The American Association of Immunologists, Inc.

PMID: 27029587 [PubMed - as supplied by publisher]