Immunological Homeostasis at the Ovine Placenta May Reflect the Degree of Maternal Fetal Interaction.

Sean R Wattegedera,Nicholas M Wheelhouse,Julian Pearce,Mariya I Goncheva,Julio Benavides,Laura E Doull,Keith Ballingall,Javier Palarea-Albaladejo,Donna M Watson,Colin J Mcinnes,Gary Entrican

doi:10.3389/fimmu.2018.03025

Abstract

Successful mammalian pregnancies are a result of complex physiological, endocrinological, and immunological processes that combine to create an environment where the mother is tolerant to the semi-allogeneic fetus. Our knowledge of the mechanisms that contribute to maternal tolerance is derived mainly from human and murine studies of haemochorial placentation. However, as this is the most invasive type of placentation it cannot be assumed that identical mechanisms apply to the less invasive epitheliochorial placentation found in other species such as ruminants. Here, we examine three features associated with reproductive immune regulation in a transformed ovine trophoblast cell line and ex-vivo ovine reproductive tissues collected at term, namely: major histocompatibility complex (MHC) expression, Indoleamine 2,3 dioxygenase-1 (IDO-1) expression, and Natural Killer (NK) cell infiltration. High levels of MHC class I protein expression were detected at the surface of the trophoblast cell line using a pan-MHC class I specific monoclonal antibody. The majority of MHC class I transcripts isolated from the cell line clustered with classical MHC alleles. Transcriptional analysis of placental tissues identified only classical MHC class I transcripts. We found no evidence of constitutive transcription of IDO-1 in either the trophoblast cell line or placental tissues. Ex-vivo tissues collected from the materno-fetal interface were negative for cells expressing NKp46/NCR1. Collectively, these observations suggest that the relatively non-invasive synepitheliochorial placentation found in sheep has a more limited requirement for local immunoregulation compared to the more invasive haemochorial placentation of primates and rodents.

Highlights

Much of our current knowledge of mammalian reproductive immunology is derived from studies in primates and rodents that share a haemochorial placenta
We report on the transcriptional expression of major histocompatibility complex (MHC) class I and IDO-1 in ovine placental tissues collected at full term and the ovine AH-1 trophoblast cell line [derived close to full-term, immortalized, and characterized by Haldorson et al [12]] and the presence of NKp46/NCR1+ve cells in ovine placental tissue in comparison to what is known for haemochorial placentation
As no monoclonal antibody (mAb) are available to discriminate between classical and non-classical MHC class I molecules in sheep, we employed transcriptional analyses to determine the nature of the MHC class I molecules expressed by the AH-1 cells

Summary

Introduction

Much of our current knowledge of mammalian reproductive immunology is derived from studies in primates and rodents that share a haemochorial placenta. Haemochorial placentation is a highly invasive process resulting in direct contact between the fetal trophoblast and the maternal decidua and blood [1]. Sheep, and other ruminants have synepitheliochorial placentation, where the uterine epithelium remains largely intact, resulting in a greater separation between the maternal and fetal cell layers. These layers are interspersed with syncytial plaques representing fusion of maternal and fetal cells which is unique to ruminants [2]. Little is known about the expression of these molecules and cells in the synepitheliochorial placentation in sheep, a reflection of the paucity of ovine immunological reagents to define these interactions [reviewed by [9]]

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