title: Pneumococcal Surface Protein A Plays a Major Role in Streptococcus pneumoniae-Induced Immunosuppression.
abstract: Intact, inactivated Streptococcus pneumoniae [including the unencapsulated S. 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 the S. pneumoniae cell wall, and lipoteichoic acid in the S. pneumoniae membrane were previously reported to be immunosuppressive when derived from filarial parasites, we determined whether R36A lacking PC (R36A(pc-)) was inhibitory. Indeed, although R36A(pc-) 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 R36A(pc-) 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 various S. pneumoniae mutants, each genetically deficient in one of the CBPs, demonstrated that only S. pneumoniae lacking 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 of S. pneumoniae.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; Department of Biological Sciences, Birla Institute of Technology and Sciences, Pilani 333031, India;
authors.lastname: Saumyaa
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, CO 80206;
authors.forename: Lindsey
authors.initials: L
authors.lastname: Pujanauski
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
authors.forename: Jesus
authors.identifier: 0000-0003-2278-382X
authors.initials: J
authors.lastname: Colino
authors.affiliation: Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and.
authors.forename: Michael
authors.identifier: 0000-0002-0714-3157
authors.initials: M
authors.lastname: Flora
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, CO 80206;
authors.forename: Raul M
authors.identifier: 0000-0002-5969-5957
authors.initials: RM
authors.lastname: Torres
authors.affiliation: Department of Infectious Disease, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Elaine
authors.identifier: 0000-0003-0349-8716
authors.initials: E
authors.lastname: Tuomanen
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; clifford.snapper@usuhs.edu.
authors.forename: Clifford M
authors.identifier: 0000-0001-7724-5186
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007166:Immunosuppressive Agents; D051379:Mice; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D010504:Periodic Acid / Q000494:pharmacology; D010767:Phosphorylcholine / Q000276:immunology* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D014357:Trypsin / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C051592:pneumococcal surface protein A; D010504:Periodic Acid; D010767:Phosphorylcholine; D010047:Ovalbumin; C009288:metaperiodate; D014357:Trypsin