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-μm 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.

Immunosuppressive Property within the Streptococcus pneumoniae Cell Wall That Inhibits Generation of T Follicular Helper, Germinal Center, and Plasma Cell Response to a Coimmunized Heterologous Protein

“…Little is known, however, regarding the immunologic consequences of simultaneous exposure to the immune system of the intact pathogen and these soluble antigens. We previously demonstrated that coimmunization with intact R36A resulted in a significantly reduced IgG response to a number of soluble TD antigens (17). In the present study, we investigated the mechanism of this inhibitory effect using R36A and soluble cOVA as the basis for the experimental system.…”

“…We previously demonstrated that an unencapsulated S. pneumoniae strain (R36A) inhibited IgG responses to a number of soluble proteins coinjected into mice i.p. in the presence of alum plus CpG-ODN adjuvant (17). CpG-ODN, a TLR9 agonist (22), significantly enhances antibody responses to soluble proteins in alum (23), thus making alum plus CpG-ODN a more effective adjuvant than alum alone.…”

“…Alum (Allhydrogel; 2%) was obtained from Brenntag Biosector (Denmark). A stimulatory 30-mer CpG-containing oligodeoxynucleotide (CpG-ODN) was synthesized (19), and a truncated (amino acids 1 to 470) Epstein-Barr virus (EBV) envelope glycoprotein (gp350) was expressed in Sf9 insect cells and purified (17).…”

“…in the presence of alum plus CpG-containing oligodeoxynucleotides (CpG-ODN) as an adjuvant (17). In contrast, soluble conjugate vaccine had no effect on the IgG response to a pneumococcal protein expressed by the intact bacterium.…”

Immune Regulatory Effects of Enteromorphaclathrata Polysaccharides on Nd Attenuated Vaccine in a Chicken Model Infected with Reticuloendotheliosis Virus

“…Changes in serum antibody titers can accurately and directly reflect humoral immunity (Chattopadhyay et al 2009). The serum antibody titer against ND of Group III was significantly higher than that of other groups (p<0.01), also indicating that EPScan enhance antibody titers stimulated by vaccine and extend the antibody peak period.…”