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Toxins 2013, 5(5), 926-938; doi:10.3390/toxins5050926

Effects of Clostridium difficile Toxin A and B on Human T Lymphocyte Migration

1
Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
2
Cangene Corporation, Winnipeg, MB R3T 2N2, Canada
3
Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
4
Department of Biosystems Engineering, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
5
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
6
BD Biosciences, La Jolla, CA 92121, USA
7
Department of Biological Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
*
Author to whom correspondence should be addressed.
Received: 12 January 2013 / Revised: 27 March 2013 / Accepted: 23 April 2013 / Published: 3 May 2013
(This article belongs to the Special Issue Novel Properties of Well-Characterized Toxins)
View Full-Text   |   Download PDF [1621 KB, 6 May 2013; original version 3 May 2013]   |  

Abstract

Bacterial products such as toxins can interfere with a variety of cellular processes, leading to severe human diseases. Clostridium difficile toxins, TcdA and TcdB are the primary contributing factors to the pathogenesis of C. difficile-associated diseases (CDAD). While the mechanisms for TcdA and TcdB mediated cellular responses are complex, it has been shown that these toxins can alter chemotactic responses of neutrophils and intestinal epithelial cells leading to innate immune responses and tissue damages. The effects of C. difficile toxins on the migration and trafficking of other leukocyte subsets, such as T lymphocytes, are not clear and may have potential implications for adaptive immunity. We investigated here the direct and indirect effects of TcdA and TcdB on the migration of human blood T cells using conventional cell migration assays and microfluidic devices. It has been found that, although both toxins decrease T cell motility, only TcdA but not TcdB decreases T cell chemotaxis. Similar effects are observed in T cell migration toward the TcdA- or TcdB-treated human epithelial cells. Our study demonstrated the primary role of TcdA (compared to TcdB) in altering T cell migration and chemotaxis, suggesting possible implications for C. difficile toxin mediated adaptive immune responses in CDAD.
Keywords: C. difficile toxin A and B; human T lymphocyte; cell migration; chemotaxis; microfluidic device C. difficile toxin A and B; human T lymphocyte; cell migration; chemotaxis; microfluidic device
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Wu, D.; Joyee, A.G.; Nandagopal, S.; Lopez, M.; Ma, X.; Berry, J.; Lin, F. Effects of Clostridium difficile Toxin A and B on Human T Lymphocyte Migration. Toxins 2013, 5, 926-938.

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