title: Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes.
abstract: BACKGROUND
  Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone.
  
  
  RESULTS
  Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81-176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone.
  
  
  CONCLUSIONS
  The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk.
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH, 44691, USA. sanad.1@buckeyemail.osu.edu.|Current address: Division of Microbiology, National Center for Toxiocological Research, US Food and Drug Administration, Jefferson, USA. sanad.1@buckeyemail.osu.edu.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Sanad
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH, 44691, USA. jung.221@osu.edu.
authors.forename: Kwonil
authors.initials: K
authors.lastname: Jung
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH, 44691, USA. ikashoma@yahoo.com.
authors.forename: Isaac
authors.initials: I
authors.lastname: Kashoma
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH, 43220, USA. Xiaoli.Zhang@osumc.edu.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH, 44691, USA. Kassem.4@osu.edu.
authors.forename: Issmat I
authors.initials: II
authors.lastname: Kassem
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH, 44691, USA. saif.1@osu.edu.
authors.forename: Yehia M
authors.initials: YM
authors.lastname: Saif
authors.affiliation: Food Animal Health Research Program (FAHRP), Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH, 44691, USA. rajashekara.2@osu.edu.|Veterinary Preventive Medicine Department, The Ohio State University, 1680 Madison Avenue, Columbus, OH, 43220, USA. rajashekara.2@osu.edu.
authors.forename: Gireesh
authors.initials: G
authors.lastname: Rajashekara
mesh_terms: D000031:Abortion, Septic / Q000209:etiology / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D000034:Abortion, Veterinary / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D002169:Campylobacter Infections / Q000150:complications / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D016123:Campylobacter jejuni; D004716:Endometritis / Q000382:microbiology / Q000473:pathology / Q000662:veterinary; D005260:Female; D020411:Oligonucleotide Array Sequence Analysis / Q000662:veterinary; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D012756:Sheep / Q000382:microbiology; D012757:Sheep Diseases / Q000382:microbiology* / Q000473:pathology; D059467:Transcriptome