Abstract
Neospora caninum is an intracellular protozoan parasite which is a major cause of abortion in cattle worldwide. It forms persistent infections which recrudesce during pregnancy leading to foetal infection and in a proportion of cases, abortion. The mechanisms underlying abortion are not understood. In this study, recrudescence of a persistent infection in eight naturally infected cows occurred between 20 and 33 weeks of gestation. Animals were killed at the time of recrudescence and parasites were detected in the placentae and foetuses. An active maternal immune response consisting of an infiltration of CD4+ and CD8+ T cells and a 46–49 fold increase in interferon-γ and interleukin-4 mRNA was detected. Other cytokines, notably interleukin-12 p40, interleukin-10 and tumour necrosis factor-α were also significantly increased and Major Histocompatibility Class II antigen was expressed on maternal and foetal epithelial and stromal fibroblastoid cells. Significantly, despite the presence of an active maternal immune response in the placenta, all the foetuses were alive at the time of maternal euthanasia. There was evidence of parasites within foetal tissues; their distribution was restricted to the central nervous system and skeletal muscle and their presence was associated with tissue necrosis and a non-suppurative inflammatory response involving lymphocytes and macrophages, irrespective of the gestational age of the foetus. Whilst an active maternal immune response to a pathogen in the placenta is generally considered to be damaging to the foetal trophoblast, our findings suggest that the presence of a parasite-induced maternal immune response in the placenta is not detrimental to foetal survival but may contribute to the control of placental parasitosis.
Highlights
Mammalian pregnancy has long been regarded as a form of ‘allogeneic graft’ with the foetus ‘parasitising’ the female uterus necessitating a suppression or modulation of the maternal immune response [1,2]
More recently it has been suggested that the interaction between the foetal trophoblast and the maternal immune system is a supportive, regulatory interaction orchestrated by the foetal trophoblast with maternal immune cells such as uterine NK cells, dendritic cells and monocytes/ macrophages recruited into the placenta to enable its development and function [3]
Recrudescence occurred after 20 weeks of gestation in all the animals; our previous work suggests that if recrudescence occurs before 20 weeks foetal death ensues rapidly, but if recrudescence occurs in the second half of gestation, the foetus survives to term [22]
Summary
Mammalian pregnancy has long been regarded as a form of ‘allogeneic graft’ with the foetus ‘parasitising’ the female uterus necessitating a suppression or modulation of the maternal immune response [1,2]. For example infection with pathogens such as Listeria monocytogenes, Chlamydophila abortus, Brucella spp or Toxoplasma gondii can have serious consequences in pregnancy [5,6,7,8] These pathogens are normally controlled by a type 1 immune response and it has been suggested that activated maternal T cells and associated T helper 1 (Th1) cytokines, recruited to control infection, have a detrimental effect on foetal survival and/or placental function [9,10]. Transplacental transmission (TPT) is a major feature of N. caninum infection and can occur following recrudescence of a persistent infection during pregnancy (endogenous TPT), or following de novo infection by ingestion of the oocyst stage of the parasite by a pregnant cow (exogenous TPT) [12] Both forms of TPT can result in foetal death or birth of clinically normal but persistently infected (PI) calves. It is widely accepted that recrudescence of a persistent infection during pregnancy is the most common route of TPT and that the majority of persistently infected cattle acquire infection before birth [13]
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