Abstract
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 (P = .006). 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1464-1470 |
| Number of pages | 7 |
| Journal | Journal of Infectious Diseases |
| Volume | 193 |
| Issue number | 10 |
| DOIs | |
| State | Published - May 15 2006 |
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ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Immunology
Cite this
Reduced gene expression of intestinal α-defensins predicts diarrhea in a cohort of African adults. / Kelly, Paul; Bajaj-Elliott, Mona; Katubulushi, Max; Zulu, Isaac; Poulsom, Richard; Feldman, Roger A.; Bevins, Charles L; Dhaliwal, Winnie.
In: Journal of Infectious Diseases, Vol. 193, No. 10, 15.05.2006, p. 1464-1470.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduced gene expression of intestinal α-defensins predicts diarrhea in a cohort of African adults
AU - Kelly, Paul
AU - Bajaj-Elliott, Mona
AU - Katubulushi, Max
AU - Zulu, Isaac
AU - Poulsom, Richard
AU - Feldman, Roger A.
AU - Bevins, Charles L
AU - Dhaliwal, Winnie
PY - 2006/5/15
Y1 - 2006/5/15
N2 - 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 (P = .006). 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.
AB - 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 (P = .006). 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.
UR - http://www.scopus.com/inward/record.url?scp=33646359941&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646359941&partnerID=8YFLogxK
U2 - 10.1086/503747
DO - 10.1086/503747
M3 - Article
C2 - 16619196
AN - SCOPUS:33646359941
VL - 193
SP - 1464
EP - 1470
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 10
ER -