title: Arginase-1-expressing macrophages are dispensable for resistance to infection with the gastrointestinal helminth Trichuris muris.
abstract: Alternatively activated macrophages (AAMs) have key roles in the immune response to a variety of gastrointestinal helminths such as Heligmosomoides bakeri and Nippostrongylus brasiliensis. In addition, AAMs have been implicated in the resolution of infection-induced pathology in Schistosoma mansoni infection. AAMs exert their activity in part via the enzyme arginase-1 (Arg1), which hydrolyses L-arginine into urea and ornithine, and can supply precursor substrate for proline and polyamine production. Trichuris muris is a worm that resides in the large intestine with resistance being characterized by a Th2 T-cell response, which drives alternatively activated macrophage production in the local environment of the infection. To investigate the role of AAMs in T. muris infection, we used independent genetic and pharmacologic models of arginase deficiency. In acute infection and Th2-dominated immunity, arginase-deficient models expelled worms normally. Macrophage-Arg1-deficient mice showed cytokine and antibody levels comparable to wild-type animals in acute and chronic infection. We also found no role for AAMs and Arg1 in infection-induced pathology in the response to T. muris in either chronic (Th1 dominated) or acute (Th2 dominated) infections. Our data demonstrate that, unlike other gastrointestinal helminths, Arg1 expression in AAMs is not essential for resistance to T. muris in effective resolution of helminth-induced inflammation.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bowcutt
authors.forename: L V
authors.initials: LV
authors.lastname: Bell
authors.forename: M
authors.initials: M
authors.lastname: Little
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Booth
authors.forename: P J
authors.initials: PJ
authors.lastname: Murray
authors.forename: K J
authors.initials: KJ
authors.lastname: Else
authors.forename: S M
authors.initials: SM
authors.lastname: Cruickshank
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006651:Histocytochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012376:Rodent Diseases / Q000276:immunology / Q000469:parasitology; D014257:Trichuriasis / Q000276:immunology* / Q000469:parasitology; D014258:Trichuris / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D016207:Cytokines; C544448:Arg1 protein, mouse; D001119:Arginase