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15 May 2006

Volume 193, Number 10
The Journal of Infectious Diseases 2006;193:1464–1470
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2006/19310-0018$15.00
DOI: 10.1086/503747
MAJOR ARTICLE

Reduced Gene Expression of Intestinal α‐Defensins Predicts Diarrhea in a Cohort of African Adults

Paul Kelly,1,2,5

Mona Bajaj‐Elliott,1,3

Max Katubulushi,5

Isaac Zulu,5

Richard Poulsom,4

Roger A. Feldman,1

Charles L. Bevins,6 and

Winnie Dhaliwal1

1Centre for Adult and Paediatric Gastroenterology, Institute of Cell and Molecular Science, Barts and The London School of Medicine, 2Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, 3Infectious Diseases and Microbiology, Institute of Child Health, and 4Cancer Research UK, Lincoln’s Inn, London, United Kingdom; 5University of Zambia School of Medicine, Lusaka, Zambia; 6Department of Medical Microbiology and Immunology, University of California, Davis

Background.Human defensin (HD) 5 and HD6, both Paneth cell α‐defensins, contribute to the antimicrobial barrier against intestinal infection. We have previously demonstrated that levels of both HD5 and HD6 mRNA were reduced in adults living in urban Zambia, compared with those in adults living in London. The aim of the present study was to determine, during 2 years of follow‐up, whether α‐defensin expression in Zambian adults is related to susceptibility to diarrhea.

Methods.We analyzed intestinal biopsy samples from a longitudinal cohort study conducted in 83 Zambian adults by quantitative reverse‐transcription polymerase chain reaction, Western blotting, immunohistochemistry, and in situ hybridization, and we measured the incidence of diarrhea.

Results.Levels of HD5 and HD6 mRNA in Paneth cells varied between participants, over time, and seasonally and were strongly correlated with mucosal architecture. Gene expression was almost exclusively restricted to Paneth cells. The median (interquartile range) HD5 mRNA level was 6.0 (5.6–6.7) log10 transcripts/μg of total RNA among 18 participants who experienced diarrhea within 2 months after biopsy‐sample collection, compared with 6.8 (6.2–7.3) log10 transcripts/μg of total RNA among 94 participants who did not ( ). A similar observation was made for HD6.

Conclusions.These data indicate that intestinal α‐defensin expression is dynamic and seasonal and suggest that susceptibility to intestinal infection is related to α‐defensin expression.

Received 19 August 2005; accepted 17 November 2005; electronically published 12 April 2006.

Reprints or correspondence: Dr. Paul Kelly, Centre for Adult and Paediatric Gastroenterology, Institute of Cell and Molecular Science, Barts and The London School of Medicine, Queen Mary, University of London, Turner St., London E1 2AD (); or, Dr. Paul Kelly, Tropical Gastroenterology and Nutrition Group, Dept. of Medicine, University of Zambia School of Medicine, University Teaching Hospital, PO Box 50398, Ridgeway, Lusaka, Zambia ().

Cited by

W. Dhaliwal, P. Kelly, M. Bajaj-Elliott. (2009) Differential effects of Staphylococcal enterotoxin B-mediated immune activation on intestinal defensins. Clinical & Experimental Immunology 156:2, 263-270
Online publication date: 1-Jun-2009.
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Sara M Dann, Lars Eckmann. (2007) Innate immune defenses in the intestinal tract. Current Opinion in Gastroenterology 23:2, 115???120
Online publication date: 1-Apr-2007.
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Jan Wehkamp, J??rgen Schauber, Eduard F Stange. (2007) Defensins and cathelicidins in gastrointestinal infections. Current Opinion in Gastroenterology 23:1, 32???38
Online publication date: 1-Feb-2007.
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Jan Wehkamp, Eduard F Stange. (2006) Paneth cells and the innate immune response. Current Opinion in Gastroenterology 22:6, 644???650
Online publication date: 1-Dec-2006.
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  • Presented in part: Gordon Research Conference on Antimicrobial Peptides, Ventura, California, 6–11 March 2005 (poster).

    Potential conflicts of interest: none reported.

    Financial support: Wellcome Trust (grant 056481).

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