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Infection and Immunity, May 2007, p. 2343-2350, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01900-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Broad Up-Regulation of Innate Defense Factors during Acute Cholera{triangledown}

Carl-Fredrik Flach,1 Firdausi Qadri,2 Taufiqur R. Bhuiyan,2 Nur H. Alam,2 Eva Jennische,3 Ivar Lönnroth,4 and Jan Holmgren1*

Institute of Biomedicine, Department of Microbiology and Immunology, and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Göteborg, Sweden,1 International Centre for Diarrhoeal Disease Research, Bangladesh, Centre for Health and Population Research, Dhaka, Bangladesh,2 Institute of Biomedicine, Department of Anatomy and Cell Biology, Göteborg University, Göteborg, Sweden,3 Institute of Biomedicine, Department of Clinical Bacteriology, Göteborg University, Göteborg, Sweden4

Received 1 December 2006/ Returned for modification 10 January 2007/ Accepted 5 February 2007

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 ({alpha}1-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.

* Corresponding author. Mailing address: Institute of Biomedicine, Department of Microbiology and Immunology, Göteborg University, Box 435, 40530 Göteborg, Sweden. Phone: 46-31-7736200. Fax: 46-31-7736210. E-mail: jan.holmgren{at}microbio.gu.se

{triangledown} Published ahead of print on 16 February 2007.

Editor: A. D. O'Brien

Infection and Immunity, May 2007, p. 2343-2350, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01900-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bhuiyan, T. R., Lundin, S. B., Khan, A. I., Lundgren, A., Harris, J. B., Calderwood, S. B., Qadri, F. (2009). Cholera Caused by Vibrio cholerae O1 Induces T-Cell Responses in the Circulation. Infect. Immun. 77: 1888-1893 [Abstract] [Full Text]  
  • de la Rosa, G., Yang, D., Tewary, P., Varadhachary, A., Oppenheim, J. J. (2008). Lactoferrin Acts as an Alarmin to Promote the Recruitment and Activation of APCs and Antigen-Specific Immune Responses. J. Immunol. 180: 6868-6876 [Abstract] [Full Text]  


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