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Broad up-regulation of innate defense factors during acute cholera.

Journal article
Authors Carl-Fredrik Flach
Firdausi Qadri
Taufiqur Rahman Bhuiyan
N. H. Alam
Eva Jennische
Ivar Lönnroth
Jan Holmgren
Published in Infection and immunity
Volume 75
Issue 5
Pages 2343-50
ISSN 0019-9567
Publication year 2007
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Biomedicine, Department of Infectious Medicine
Pages 2343-50
Language en
Keywords Acute Disease, Caco-2 Cells, Cholera, immunology, microbiology, physiopathology, Cholera Toxin, immunology, Chronic Disease, Gene Expression Regulation, Humans, Immunity, Natural, Intestinal Mucosa, immunology, Oligonucleotide Array Sequence Analysis, methods, Proteins, genetics, metabolism, Up-Regulation, Vibrio cholerae, immunology
Subject categories Medical and Health Sciences


We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute- and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data. An immunohistochemical analysis revealed increased expression of lactoferrin in lamina propria cells and increased expression of CD55 in epithelial cells, whereas increased expression of the SERPINA3 protein (alpha1-antichymotrypsin) was detected in both lamina propria and epithelial cells during acute cholera. The expression pattern of CD55 and SERPINA3 in cholera toxin (CT)-stimulated Caco-2 cells was the same as the pattern found in the intestinal mucosa during acute cholera, indicating that the activation of the CD55 and SERPINA3 genes in intestinal epithelium was induced by CT. In conclusion, during acute cholera infection, innate defense mechanisms are switched on to an extent not described previously. Both direct effects of CT on the epithelial cells and changes in the lamina propria cells contribute to this up-regulation.

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