Eukaryotic Cell doi:10.1128/EC.00371-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Blastocystis Contains Cysteine Proteases that Mediate Interleukin-8 Response from Human Intestinal Epithelial Cells in a NFkB-dependent Manner
Manoj K Puthia,
Jia Lu,
and
Kevin S W Tan*
Laboratory of Molecular and Cellular Parasitology, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597; Defence Medical and Environmental Research Institute, DSO National Laboratories, 27, Medical Drive, DSO (Kent Ridge), Singapore 117510
* To whom correspondence should be addressed. Email:
mictank{at}nus.edu.sg.
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Abstract |
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Blastocystis is a ubiquitous enteric protozoan found in the intestinal tract of humans and a wide range of animals. Accumulating evidence over the last decade suggests association of Blastocystis with gastrointestinal disorders involving diarrhea, abdominal pain, constipation, nausea and fatigue. Clinical and experimental studies have associated Blastocystis with intestinal inflammation and it has been shown that Blastocystis has potential to modulate the host immune response. Blastocystis is also reported to be an opportunistic pathogen in immunosuppressed patients especially suffering with AIDS. However, nothing is known about the parasitic virulence factors and early events following host-parasite interactions. In the present study, we investigated the molecular mechanism by which Blastocystis activates IL-8 gene expression in human colonic epithelial T84 cells. We demonstrate for the first time that cysteine proteases of B. ratti WR1, a zoonotic isolate, can activate IL-8 gene expression in human colonic epithelial cells. Furthermore we show that NF-
B activation is involved in the production of IL-8. In addition, our findings show that the antiprotozoal drug metronidazole treatment can avert IL-8 production induced by Blastocystis ratti WR1. We also show for the first time that central vacuole of Blastocystis may function as a reservoir for cysteine proteases. Our findings will contribute to understanding the pathobiology of a poorly studied parasite for which public health importance is increasingly recognized.
