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Infection and Immunity, February 2008, p. 678-684, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.00732-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Possible Role for Toll-Like Receptors in Interaction of Fasciola hepatica Excretory/Secretory Products with Bovine Macrophages{triangledown}

Robin J. Flynn* and Grace Mulcahy

Veterinary Sciences Centre, School of Agriculture, Food Science, and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin 4, Ireland

Received 30 May 2007/ Returned for modification 8 September 2007/ Accepted 27 November 2007

Alternative activation of macrophages (M{phi}) during helminth infection is a characteristic feature of the host immune response. Alternatively activated macrophages (AAM{phi}) are distinguished from others by high arginase 1 (Arg-1) activity, low nitric oxide (NO), and high interleukin 10 (IL-10) production. In murine models, these cells have been shown to possess anti-inflammatory properties. They have also been implicated in exacerbating a subsequent infection with a secondary pathogen. In this study we used cattle experimentally infected with Fasciola hepatica to monitor the kinetics of IL-4 and IL-10 over the course of infection. Using naïve M{phi} in vitro, we examined the effects of exposure to F. hepatica excretory/secretory products (FhepES) alone or in combination with IL-4. Our results suggest that FhepES may work in combination with IL-4 to produce AAM{phi}. The effects of FhepES on the subsequent responses to lipopolysaccharide (LPS) and purified protein derivative from Mycobacterium bovis (PPD-B), which are bovine Toll-like receptor 4 (TLR4) and TLR2 antagonists, respectively, were also examined. We found that M{phi} stimulated with FhepES together with LPS or PPD-B have reduced NO or gamma interferon production, respectively. The ability of FhepES to produce AAM{phi} was found to be heat labile and partially dependent on glycan residues. A possible role for TLR recognition is discussed.

* Corresponding author. Mailing address: Veterinary Sciences Centre, School of Agriculture, Food Science, and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin 4, Ireland. Phone: 00 353 (01) 716 6135. Fax: 00 353 (01) 716 6185. E-mail: robin.flynn{at}ucd.ie

{triangledown} Published ahead of print on 10 December 2007.

Editor: J. F. Urban, Jr.

Infection and Immunity, February 2008, p. 678-684, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.00732-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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