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Intact Bacteria Inhibit the Induction of Humoral Immune Responses to Bacterial-Derived and Heterologous Soluble T Cell-Dependent Antigens¹

Gouri Chattopadhyay^*, Quanyi Chen^*, Jesus Colino^*, Andrew Lees and Clifford M. Snapper^2,*

^* Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and Fina BioSolutions, Rockville, MD 20850

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by National Institutes of Health Grant 1R01 AI49192 (to C.M.S.) and the Uniformed Services University of the Health Sciences Dean’s Research and Education Endowment Fund (to C.M.S.), and by funding from the intramural program of the National Human Genome Research Institute (to P.L.S.).

Opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences.

² Address correspondence and reprint requests to Dr. Clifford M. Snapper, Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. E-mail address: csnapper{at}usuhs.mil

³ Abbreviations used in this paper: Pn, intact Streptococcus pneumoniae; PS, polysaccharide; MZB, marginal zone B; FDC, follicular dendritic cell; FB, follicular B; TI, T cell independent; TD, T cell dependent; GC, germinal center; PPS14, pneumococcal capsular polysaccharide, serotype 14; PspA, pneumococcal surface protein A; cOVA, chicken OVA; Pn14, intact S. pneumoniae, capsular type 14; R36A, unencapsulated variant of S. pneumoniae, capsular polysaccharide, serotype 2 (strain D39); CBP, choline-binding protein; CpG-ODN, CpG-containing oligodeoxynucleotide.