title: Giardia muris infection in mice is associated with a protective interleukin 17A response and induction of peroxisome proliferator-activated receptor alpha.
abstract: The protozoan parasite Giardia duodenalis (Giardia lamblia) is one of the most commonly found intestinal pathogens in mammals, including humans. In the current study, a Giardia muris-mouse model was used to analyze cytokine transcription patterns and histological changes in intestinal tissue at different time points during infection in C57BL/6 mice. Since earlier work revealed the upregulation of peroxisome proliferator-activated receptors (PPARs) in Giardia-infected calves, a second aim was to investigate the potential activation of PPARs in the intestines of infected mice. The most important observation in all mice was a strong upregulation of il17a starting around 1 week postinfection. The significance of interleukin 17A (IL-17A) in orchestrating a protective immune response was further demonstrated in an infection trial or experiment using IL-17 receptor A (IL-17RA) knockout (KO) mice: whereas in wild-type (WT) mice, cyst secretion dropped significantly after 3 weeks of infection, the IL-17RA KO mice were unable to clear the infection. Analysis of the intestinal response further indicated peroxisome proliferator-activated receptor alpha (PPARα) induction soon after the initial contact with the parasite, as characterized by the transcriptional upregulation of ppara itself and several downstream target genes such as pltp and cpt1. Overall, PPARα did not seem to have any influence on the immune response against G. muris, since PPARα KO animals expressed il-17a and could clear the infection similar to WT controls. In conclusion, this study shows for the first time the importance of IL-17 production in the clearance of a G. muris infection together with an early induction of PPARα. The effect of the latter, however, is still unclear.
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Leentje
authors.initials: L
authors.lastname: Dreesen
authors.affiliation: Laboratory of Eukaryotic Gene Expression & Signal Transduction, Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: De Bosscher
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Grietje
authors.initials: G
authors.lastname: Grit
authors.affiliation: Université Lille 2, INSERM U1011, European Genomic Institute for Diabetes (EGID), and Institut Pasteur de Lille, Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Department of Rheumatology, Erasmus University Medical Center, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
authors.affiliation: Université Lille 2, INSERM U1011, European Genomic Institute for Diabetes (EGID), and Institut Pasteur de Lille, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bauge
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium peter.geldhof@UGent.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Geldhof
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005872:Giardia / Q000276:immunology*; D005873:Giardiasis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D006651:Histocytochemistry; D020381:Interleukin-17 / Q000276:immunology*; D007422:Intestines / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics; D053722:Receptors, Interleukin-17 / Q000172:deficiency; D014158:Transcription, Genetic
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; D047493:PPAR alpha; D053722:Receptors, Interleukin-17