Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes

Abstract

BackgroundCampylobacter 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.ResultsPregnant 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-014-0274-8) contains supplementary material, which is available to authorized users.

Porcine deltacoronavirus induces apoptosis in swine testicular and LLC porcine kidney cell lines in vitro but not in infected intestinal enterocytes in vivo

“…Paraffin-embedded intestinal tissues or IF-stained LLC-PK or ST cells were prepared as described above and evaluated by a TUNEL assay kit (Roche Applied Science, Mannheim, Germany) for apoptosis according to the manufacturer's instructions and as described previously (Jung et al, 2009;Sanad et al, 2015). Three serial intestinal tissue sections cut in 3-mm sections were also tested by H&E, IF staining for the detection of PDCoV antigens, and TUNEL assay, respectively.…”

“…Three serial intestinal tissue sections cut in 3-mm sections were also tested by H&E, IF staining for the detection of PDCoV antigens, and TUNEL assay, respectively. The formalin-fixed, paraffin-embedded placentomal tissue of a healthy pregnant ewe that showed a strong positive TUNEL staining (Sanad et al, 2015), was used as a positive control of in situ TUNEL assay. The IF-stained LLC-PK or ST cells were double-stained by TUNEL assay.…”

“…1D), indicating that a few immune cells or mature enterocytes underwent apoptosis as a normal turnover process as tested. The placentomal tissue of a healthy pregnant ewe (Sanad et al, 2015), used as a positive control of in situ TUNEL assay, showed large numbers of in situ TUNEL-positive cells (Fig. 1E).…”

Diagnoses of Primary Cause of Mortality in Domestic Sheep in the North American Intermountain West

“…However, most abortions where bacteria were observed histologically were not cultured because despite being in sufficient preservation for necropsy, bacterial overgrowth or contamination was considered likely because of the condition of the tissues. These agents reported here have often been described in this order as the most common causes of ovine abortion worldwide, including the U.S., even though most of the data comes from the United Kingdom or elsewhere [5,6]. No summary reports of diagnostic results of causes of ovine abortion in the U.S. have been published for over 20 years, when C. fetus was isolated more frequently than C. jejuni and C. abortus [7].…”

“…However, causes of adult mortality also included obstructive urolithiasis, mastitis, metritis, neoplasia and trauma. Urolithiasis, mastitis, and metritis are recognized as important and common diseases in sheep, including as causes of mortality [6,14,15]. One sheep had a pituitary acidophil adenoma while another had pancreatitis.…”