title: Intact bacteria inhibit the induction of humoral immune responses to bacterial-derived and heterologous soluble T cell-dependent antigens.
abstract: During infections with extracellular bacteria, such as Streptococcus pneumoniae (Pn), the immune system likely encounters bacterial components in soluble form, as well as those associated with the intact bacterium. The potential cross-regulatory effects on humoral immunity in response to these two forms of Ag are unknown. We thus investigated the immunologic consequences of coimmunization with intact Pn and soluble conjugates of Pn-derived proteins and polysaccharides (PS) as a model. Coimmunization of mice with Pn and conjugate resulted in marked inhibition of conjugate-induced PS-specific memory, as well as primary and memory anti-protein Ig responses. Inhibition occurred with unencapsulated Pn, encapsulated Pn expressing different capsular types of PS than that present in the conjugate, and with conjugate containing protein not expressed by Pn, but not with 1-microm latex beads in adjuvant. Inhibition was long-lasting and occurred only during the early phase of the immune response, but it was not associated with tolerance. Pn inhibited the trafficking of conjugate from the splenic marginal zone to the B cell follicle and T cell area, strongly suggesting a potential mechanism for inhibition. These data suggest that during infection, bacterial-associated Ags are the preferential immunogen for antibacterial Ig responses.
authors.affiliation: Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Gouri
authors.initials: G
authors.lastname: Chattopadhyay
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Chen
authors.forename: Jesus
authors.initials: J
authors.lastname: Colino
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Snapper
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial