Possible role for Toll-like receptors in interaction of Fasciola hepatica excretory/secretory products with bovine macrophages.
Alternative activation of macrophages (Mphi) during helminth infection is a characteristic feature of the host immune response. Alternatively activated macrophages (AAMphi) 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 Mphi 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 AAMphi. 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 Mphi stimulated with FhepES together with LPS or PPD-B have reduced NO or gamma interferon production, respectively. The ability of FhepES to produce AAMphi was found to be heat labile and partially dependent on glycan residues. A possible role for TLR recognition is discussed.
Flynn
Robin J
RJ
Veterinary Sciences Centre, School of Agriculture, Food Science, and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin 4, Ireland. robin.flynn@ucd.ie
Mulcahy
Grace
G
D000818:Animals; D002417:Cattle; D005210:Fasciola hepatica / Q000276:immunology*; D015801:Helminth Proteins / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014373:Tuberculin / Q000276:immunology
D015801:Helminth Proteins; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014373:Tuberculin; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma