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

Abstract

Intact, inactivated Streptococcus pneumoniae (Pn) [including the unencapsulated strain, R36A], markedly inhibits the humoral immune response to co-immunized 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. Since phosphorylcholine (PC), a major haptenic component of teichoic acid in the Pn cell wall, and lipoteichoic acid in the Pn membrane, was previously reported to be immunosuppresive 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 co-immunized 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. Since R36Apc- also lacks choline-binding proteins (CBPs), that require PC for cell wall attachment, and since 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. Co-immunization studies using cOVA and various Pn mutants, each genetically deficient in one of the CBPs, demonstrated that only Pn lacking the CBP, pneumococcal surface protein A (PspA), 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 of Pn.

Targeting Evolutionary Conserved Oxidative Stress and Immunometabolic Pathways for the Treatment of Respiratory Infectious Diseases

“…PsrP has been described as having a role in the development of biofilms (145), and it is a lung-specific adherin. PspA, alternatively, mediates the immunosuppressive property of phosphorylcholine via inhibition of immunoglobulin G (146).…”

The choline-binding proteins PspA, PspC and LytA of Streptococcus pneumoniae and their role on host cellular adhesion and damage

“…CBPs are key players in immune evasion, virulence (12) and host pathogenicity (13)(14)(15). Their pathogenic roles range from proteolytic activities, binding of human plasma regulators, complement proteins and immune components, and cell-mediated contact to inactivate human immunoglobulins prior to nasopharyngeal colonization (16)(17)(18)(19).…”