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Infection and Immunity, January 2005, p. 166-173, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.166-173.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Thioredoxin Peroxidase Secreted by Fasciola hepatica Induces the Alternative Activation of Macrophages

Sheila Donnelly,1*,{dagger} Sandra M. O'Neill,2,{dagger} Mary Sekiya,3 Grace Mulcahy,3 and John P. Dalton1,3,4

School of Biotechnology,1 School of Nursing, Dublin City University,2 Department of Veterinary Microbiology and Parasitology, Faculty of Veterinary Medicine, University College Dublin, Dublin, Republic of Ireland,3 Institute for the Biotechnology of Infectious Diseases, University of Technology Sydney, Sydney, New South Wales, Australia4

Received 13 April 2004/ Returned for modification 23 May 2004/ Accepted 25 August 2004

Alternatively activated macrophages (AAM{phi}) are primarily associated with the chronic stages of parasitic infections and the development of a polarized Th2 response. We have shown that Fasciola hepatica infection of BALB/c mice induces a polarized Th2 response during both the latent and chronic stage of disease. The activation status of macrophages was analyzed in this model of helminth infection by evaluating the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arg1. AAM{phi} were recruited to the peritoneum of mice within 24 h of F. hepatica infection and after intraperitoneal injection of parasite excretory-secretory (ES) products. Administration of a recombinant antioxidant thioredoxin peroxidase (TPx), which is contained within the ES products, also induced the recruitment of AAM{phi} to the peritoneum. In vitro studies showed that this recombinant TPx directly converts RAW 264.7 macrophages to an alternatively activated phenotype characterized by the production of high levels of interleukin-10 (IL-10), prostaglandin E2, corresponding with low levels of IL-12. Our data suggest that the Th2 responses induced by the helminth F. hepatica are mediated through the secretion of molecules, one of which is TPx, that induce the recruitment and alternative activation of macrophages.

* Corresponding author. Mailing address: Institute for the Biotechnology of Infectious Diseases, University of Technology Sydney, Westbourne St., Gore Hill, Sydney, NSW 2065, Australia. Phone: 61(02)95144143. Fax: 61(02)95144201. E-mail: Sheila.Donnelly{at}uts.edu.au.

Editor: J. F. Urban, Jr.

{dagger} S.D. and S.M.O. contributed equally to this study.

Infection and Immunity, January 2005, p. 166-173, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.166-173.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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