IFN-γ has been shown to control C. abortus growth in ovine cells in a dose-dependent manner.26 The amount of IFN-γ that infected cells are exposed to is critical, because concentrations of around 50 U/mL or lower can induce persistent infection whereas concentrations of 200 U/mL or greater can eradicate the infection.26 Immune-mediated persistence of C. abortus has selleck chemical important implications for OEA pathogenesis and epidemiology, because persistence in
non-pregnant sheep permits pathogen survival within the host outwith periods of reproduction.18 The mechanism by which IFN-γ controls the growth of Chlamydia is not uniform across species, and furthermore there is evidence for evolution of host–pathogen interactions and evasion of the IFN-γ response by Chlamydiae
as is the case for Chlamydia muridarum in mice.27 In sheep, we know that IFN-γ-mediated control of C. abortus occurs through the activation of indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades intracellular pools of tryptophan.28C. abortus lacks all of the five genes (trpA–trpE) that comprise a functional operon required for synthesis of tryptophan from chorismate and is therefore highly susceptible to IFN-γ-induced IDO expression.29 Hence, this fits the prediction of the paradigm that host control of C. abortus is mediated through an IFN-γ TH1-type response, although to reiterate the point aforementioned, it is not yet clear whether CD4+ve T cells are the principal producers of this cytokine in immune
sheep. Placental IDO expression was first conclusively demonstrated as MEK inhibitor a mechanism for tolerizing maternal T cells to the foetus in a series of experiments involving administration of an IDO inhibitor to mice carrying syngeneic or allogeneic concepti and adoptive transfer of allospecific CD8+ve T cells.30 In contrast Interleukin-3 receptor to the intracellular IDO host defence pathway described earlier, placental IDO expression was not induced by IFN-γ but instead was found to be constitutively expressed by foetal trophoblast cells. This is not unique to mice. Constitutive IDO expression has also been described in syncytiotrophoblast of human, rhesus monkey and marmoset placenta at term.31,32 However, to date, there are no definitive reports in the literature of placental IDO expression in sheep (or other ruminants). Therein is a key question: is foetal trophoblast IDO expression associated with placental structure, particularly to the degree of foetal trophoblast invasiveness into maternal uterine tissue? The evolutionary processes that have driven the different shapes and structure of mammalian placentas remain controversial, so the answer to the IDO question may help identify factors that have influenced mammalian placental development and immunological materno–foetal interactions.