Polymeric immunoglobulin receptor in intestinal immune defense against the lumen-dwelling protozoan parasite Giardia

被引:64
作者
Davids, Barbara J.
Palm, J. E. Daniel
Housley, Michael P.
Smith, Jennifer R.
Andersen, Yolanda S.
Martin, Martin G.
Hendrickson, Barbara A.
Johansen, Finn-Eirik
Svard, Staffan G.
Gillin, Frances D.
Eckmann, Lars
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA
[3] Uppsala Univ, Dept Cell & Mol Biol, Uppsala, Sweden
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Gastroenterol & Nutr,Mattel Childrens Hosp, Los Angeles, CA 90095 USA
[5] Univ Chicago, Dept Pediat, Infect Dis Sect, Chicago, IL 60637 USA
[6] Univ Oslo, Radiumhosp Med Ctr, Rikshosp, Dept Pathol, Oslo, Norway
[7] Univ Oslo, Radiumhosp Med Ctr, Rikshosp, Inst Pathol, Oslo, Norway
关键词
D O I
10.4049/jimmunol.177.9.6281
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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, alpha-enolase, and alpha- and beta-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.
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收藏
页码:6281 / 6290
页数:10
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