Pneumococcal Choline-Binding Proteins Contain An Activity That Mediates Streptococcus Pneumoniae-Induced Immunosuppression

Abstract We previously demonstrated that intact, inactivated Streptococcus pneumoniae (strain R36A) inhibits murine IgG, T follicular helper, germinal center and plasma cell responses to co-immunized chicken ovalbumin (cOVA), whereas intact, inactivated Streptococcus agalactiae and Neisseria meningitides did not. Since phosphorylcholine (PC), reported to mediate immunosuppression by filarial organisms, was selectively expressed by R36A, we determined whether R36A lacking PC (R36APC-) lost this inhibitory activity. R36APC- indeed, exhibited a significant loss of inhibition of the anti-cOVA response. However, R36APC- is also devoid of a family of choline binding proteins (CBPs) that are attached to the bacterial cell surface via PC binding. We thus prepared CBP-depleted R36A (R36ACBP-) by stripping CBPs from the cell surface using choline chloride. R36ACBP-, which continues to express PC, also exhibited a significant reversal in inhibition of the anti-cOVA response. Inhibition of the anti-cOVA response was also mediated by isolated R36A cell walls, supernatant from choline chloride-treated R36A, and purified CBPs. In contrast, trypsinized intact R36A and trypsinized CBP-containing supernatant lost their inhibitory activity. These results suggest a novel immunosuppressive property expressed by CBPs and CBP-expressing S. pneumoniae. Studies are continuing to specifically identify this activity.