TITLE:
Bovine Endometrial Cells Mount Innate Immune Response to the Intracellular Ligands CL097 and Poly(dA:dT) Indicating Roles against Uterine Viruses
AUTHORS:
Chike F. Oguejiofor, Zhangrui Cheng, Ali A. Fouladi-Nashta, D. Claire Wathes
KEYWORDS:
Endometrium, Innate Immunity, Intracellular Ligands, Gene Expression
JOURNAL NAME:
Open Journal of Animal Sciences,
Vol.7 No.2,
April
17,
2017
ABSTRACT: Uterine infection and
endometritis cause infertility and economic losses in the cattle industry. The
innate immune response of the endometrium is critical in the elimination of
pathogenic organisms that invade the uterus in postpartum cows. This study
investigated the response of bovine endometrium to synthetic intracellular
ligands which activate innate immunity by stimulating similar receptors to
those used to recognise the presence of some viruses. Mixed primary epithelial
and stromal cell cultures were treated with 5 μg/ml of CL097 (a TLR7/8 ligand)
or 2 μg/ml of poly(dA:dT) (a DNA analogue) for either 6 h or 24 h. Cellular
responses were assessed by the mRNA expression of 18 immune-related genes and 3
endogenous reference genes by conventional PCR followed by qRT-PCR from four
replicate experiments. Bovine endometrial cells expressed the cytosolic pattern
recognition receptors (PRRs) DDX58 (RIG-I), IFIH1 (MDA5) and LRRFIP1 which act as intracellular
nucleic acid sensors. Neither ligand altered the expression of the
extra-cytosolic pattern recognition receptors (PRRs) TLR3, TLR4, TLR7 or TLR8 whereas poly(dA:dT) treatment increased the expression of IFIH1 and DDX58. Treated cells also responded to CL097 or poly(dA:dT) with a
differential up-regulation of genes involved in innate immune response
including type I interferon/antiviral response (MX1, IFNAR1),
antimicrobial activity (MUC1, SLPI) and cytokine activity (TNF, IL1B, IL8). Bovine endometrial cells
therefore express both cytosolic and extra-cytosolic intracellular PRRs and are
able to mount an innate immune response upon stimulation with intracellular
ligands. This suggests an important role for these cells in the defence against
viruses that may be present in the uterus in postpartum cows.