title: The early intestinal immune response in experimental neonatal ovine cryptosporidiosis is characterized by an increased frequency of perforin expressing NCR1(+) NK cells and by NCR1(-) CD8(+) cell recruitment.
abstract: Cryptosporidium parvum, a zoonotic protozoan parasite, causes important losses in neonatal ruminants. Innate immunity plays a key role in controlling the acute phase of this infection. The participation of NCR1+ Natural Killer (NK) cells in the early intestinal innate immune response to the parasite was investigated in neonatal lambs inoculated at birth. The observed increase in the lymphocyte infiltration was further studied by immunohistology and flow cytometry with focus on distribution, density, cellular phenotype related to cytotoxic function and activation status. The frequency of NCR1+ cells did not change with infection, while their absolute number slightly increased in the jejunum and the CD8+/NCR1- T cell density increased markedly. The frequency of perforin+ cells increased significantly with infection in the NCR1+ population (in both NCR1+/CD16+ and NCR1+/CD16- populations) but not in the NCR1-/CD8+ population. The proportion of NCR1+ cells co-expressing CD16+ also increased. The fraction of cells expressing IL2 receptor (CD25), higher in the NCR1+/CD8+ population than among the CD8+/NCR1- cells in jejunal Peyer's patches, remained unchanged during infection. However, contrary to CD8+/NCR1- lymphocytes, the intensity of CD25 expressed by NCR1+ lymphocytes increased in infected lambs. Altogether, the data demonstrating that NK cells are highly activated and possess a high cytotoxic potential very early during infection, concomitant with an up-regulation of the interferon gamma gene in the gut segments, support the hypothesis that they are involved in the innate immune response against C. parvum. The early significant recruitment of CD8+/NCR1- T cells in the small intestine suggests that they could rapidly drive the establishment of the acquired immune response.
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway. l.olsen@nmbu.no.
authors.forename: Line
authors.initials: L
authors.lastname: Olsen
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway. carolinepiercey.akesson@nmbu.no.
authors.forename: Caroline Piercey
authors.initials: CP
authors.lastname: Åkesson
authors.affiliation: Department of Food Safety & Infection Biology, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway. anne.storset@nmbu.no.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Storset
authors.affiliation: Institut National de la Recherche Agronomique, UMR1282, Infectiologie et Santé Publique, Laboratoire Apicomplexes et Immunité Muqueuse, Nouzilly, France. sonia.lamande@tours.inra.fr.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lacroix-Lamandé
authors.affiliation: Department of Food Safety & Infection Biology, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway. preben.boysen@nmbu.no.
authors.forename: Preben
authors.initials: P
authors.lastname: Boysen
authors.affiliation: Institut National de la Recherche Agronomique, UMR1282, Infectiologie et Santé Publique, Laboratoire Apicomplexes et Immunité Muqueuse, Nouzilly, France. cmetton@jouy.inra.fr.
authors.forename: Coralie
authors.initials: C
authors.lastname: Metton
authors.affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK. timothy.connelley@ed.ac.uk.
authors.forename: Timothy
authors.initials: T
authors.lastname: Connelley
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway. arild.espenes@nmbu.no.
authors.forename: Arild
authors.initials: A
authors.lastname: Espenes
authors.affiliation: Institut National de la Recherche Agronomique, UMR1282, Infectiologie et Santé Publique, Laboratoire Apicomplexes et Immunité Muqueuse, Nouzilly, France. fabrice.laurent@tours.inra.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Laurent
authors.affiliation: Institut National de la Recherche Agronomique, UMR1282, Infectiologie et Santé Publique, Laboratoire Apicomplexes et Immunité Muqueuse, Nouzilly, France. francoise.drouet@tours.inra.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Drouet
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003457:Cryptosporidiosis / Q000276:immunology* / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate; D007422:Intestines / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054353:Perforin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010581:Peyer's Patches / Q000276:immunology; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology* / Q000469:parasitology; D015854:Up-Regulation
chemical_list: D055627:Natural Cytotoxicity Triggering Receptor 1; D054353:Perforin