title: Differential regulation of protein- and polysaccharide-specific Ig isotype production in vivo in response to intact Streptococcus pneumoniae.
abstract: Adaptive humoral immunity to extracellular bacteria is largely mediated by antibody specific for both protein and polysaccharide antigens. Proteins and polysaccharides are biochemically distinct, and as a result are processed differently by the immune system, leading to different mechanistic pathways for eventual elicitation of specific Ig isotypes. Much of our current knowledge concerning the parameters underlying anti-protein and anti-polysaccharide Ig responses have come from studies using soluble, purified antigens. However, the lessons learned from these studies are not entirely applicable to the mechanisms underlying physiologic anti-protein and anti-polysaccharide Ig responses to intact bacteria. Specifically, unlike isolated, soluble antigens, intact bacteria are complex particulate immunogens in which multiple protein and polysaccharide antigens, and bacterial adjuvants (e.g. Toll-like receptor ligands) are co-expressed, indeed often physically linked. In this review, data from a series of recent studies are discussed in which heat-killed, intact Streptococcus pneumoniae was used as an immunogen to study the mechanisms underlying in vivo anti-protein and anti-polysaccharide Ig isotype induction. An unexpected role for CD4(+) T cells and dendritic cells for induction of IgG anti-polysaccharide responses by intact bacteria is discussed, and shown to have distinct mechanistic features from those that mediate anti-protein responses. The further role of cytokines, Toll-like receptors, and B cell receptor signaling in mediating these responses, and its implications for the effectiveness of anti-pneumococcal, polysaccharide-based vaccines, is also discussed.
authors.affiliation: Department of Pathology, USUHS, 4301 Jones Bridge Road, Bethesda, Maryland 20814, USA. csnapper@usuhs.mil
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D005786:Gene Expression Regulation; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000737:chemistry*; D007136:Immunoglobulins / Q000737:chemistry*; D007156:Immunologic Memory; D011008:Pneumococcal Infections / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D011135:Polysaccharides, Bacterial; D011506:Proteins; D051193:Toll-Like Receptors