HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Davids, B. J. Articles by Eckmann, L. Search for Related Content PubMed PubMed Citation Articles by Davids, B. J. Articles by Eckmann, L.

Polymeric Immunoglobulin Receptor in Intestinal Immune Defense against the Lumen-Dwelling Protozoan Parasite Giardia¹

Barbara J. Davids^*, J. E. Daniel Palm, Michael P. Housley, Jennifer R. Smith, Yolanda S. Andersen, Martin G. Martin, Barbara A. Hendrickson^¶, Finn-Eirik Johansen^||, Staffan G. Svärd, Frances D. Gillin^* and Lars Eckmann^2,

^* Department of Pathology, University of California, San Diego, CA 92103; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden; Department of Medicine, University of California San Diego, La Jolla, CA 92093; Department of Pediatrics, Division of Gastroenterology and Nutrition, Mattel Children’s Hospital, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; ^¶ Section of Infectious Diseases, Department of Pediatrics, University of Chicago, Chicago, IL 60637; and ^|| Department and Institute of Pathology, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Oslo, Norway

The polymeric Ig receptor (pIgR) is conserved in mammals and has an avian homologue, suggesting evolutionarily important functions in vertebrates. It transports multimeric IgA and IgM across polarized epithelia and is highly expressed in the intestine, yet little direct evidence exists for its importance in defense against common enteric pathogens. In this study, we demonstrate that pIgR can play a critical role in intestinal defense against the lumen-dwelling protozoan parasite Giardia, a leading cause of diarrheal disease. The receptor was essential for the eradication of Giardia when high luminal IgA levels were required. Clearance of Giardia muris, in which IgA plays a dominant role, was severely compromised in pIgR-deficient mice despite significant fecal IgA output at 10% of normal levels. In contrast, eradication of the human strain Giardia lamblia GS/M, for which adaptive immunity is less IgA dependent in mice, was unaffected by pIgR deficiency, indicating that pIgR had no physiologic role when lower luminal IgA levels were sufficient for parasite elimination. Immune IgA was greatly increased in the serum of pIgR-deficient mice, conferred passive protection against Giardia, and recognized several conserved giardial Ags, including ornithine carbamoyltransferase, arginine deiminase, -enolase, and - and -giardins, that are also detected in human giardiasis. Corroborative observations were made in mice lacking the J chain, which is required for pIgR-dependent transepithelial IgA transport. These results, together with prior data on pIgR-mediated immune neutralization of luminal cholera toxin, suggest that pIgR is essential in intestinal defense against pathogenic microbes with high-level and persistent luminal presence.

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 work was supported by National Institutes of Health Grants DK35108, RR17030, AI56075, and HD34706.

² Address correspondence and reprint requests to Dr. Lars Eckmann, University of California San Diego, Department of Medicine 0063, 9500 Gilman Drive, La Jolla, CA 92093-0063. E-mail address: leckmann{at}ucsd.edu

³ Abbreviations used in this paper: pIgR, polymeric Ig receptor; ADI, arginine deiminase; OCT, ornithine carbamoyltransferase; SIgA, secretory IgA.