The placenta: a main role in congenital toxoplasmosis? Florence Robert-Gangneux 1, 2 , Jean-Benjamin Murat 3, 4 , He ´ le ` ne Fricker-Hidalgo 3, 4 , Marie-Pierre Brenier-Pinchart 3, 4 , Jean-Pierre Gangneux 1, 2 and Herve ´ Pelloux 3, 4 1 Laboratoire de Parasitologie–Mycologie, Centre Hospitalier et Universitaire de Rennes, Rennes, France 2 EA4427-SERAIC, IRSET (Institut de Recherche en Sante ´ Environnement Travail), Universite ´ Rennes 1, Rennes, France 3 Laboratoire de Parasitologie–Mycologie, Centre Hospitalier et Universitaire de Grenoble, Grenoble, France 4 Laboratoire Adaptation et Pathoge ´ nie des Microorganismes, UMR 5163 CNRS-UJF, Universite ´ Joseph Fourier, Grenoble, France Systemic infections, such as toxoplasmosis, acquired during pregnancy can lead to placental infection and have profound effects on the mother-to-child relation- ship and the success of pregnancy. Placental permeabil- ity to Toxoplasma gondii is a main parameter that determines parasite transmission to the foetus, and the use of antibiotics to decrease placental parasite load and prevent congenital toxoplasmosis has been sug- gested for decades. Although parasitological examina- tion of the placenta at birth is commonly used to diagnose neonatal congenital toxoplasmosis, this ap- proach can be controversial. Here we argue in favour of placental examination for both diagnostic and epide- miological purposes. The consequences of Toxoplasma infection during pregnancy Infection with the intracellular protozoan parasite Toxo- plasma gondii is one of the most frequent worldwide parasitic infections. Its widespread distribution in warm-blooded animals, as an intermediate host for its asexual replicating stages, offers a range of opportunities for human infection through undercooked meat or raw vegetables contaminated with oocysts spread by definitive hosts, i.e. cats or other Felidae in some parts of the world. Infection is usually asymptomatic when it occurs in an immunocompetent subject. However, the pathophysiology of toxoplasmosis in humans is far more complex when primary infection is acquired during pregnancy; it then results in congenital infection of the foetus in 30% of cases, which can result in brain or eye damage, with the degree of severity dependent on gestational age and the use, or not, of preventive protocols. The placenta prevents the passage of infectious agents towards the foetal compartment more effectively at the beginning of pregnancy than at the end. It is a key tissue in the mother-to-foetus relationship, not only because of its trophic role but also because it provides the tolerant im- mune microenvironment necessary for gestation [1]. Dur- ing primary infection, parasites cross the intestinal barrier and invade monocyte cells in contact with the lamina propria, which allow them to disseminate through the blood flow towards virtually all organs, including placenta [2]. Infection of the placental tissue can result in a pla- centitis and can lead to subsequent infection of trophoblast cells, which are at the interface with the foetal compart- ment and may let the parasites proceed [3]. This important process has two main consequences: (i) placental infection may adversely affect this tenuous equilibrium between maternal and foetal compartments; and (ii) the placenta is directly involved in parasite transmission to the foetus, making it a main therapeutic and diagnostic target. This opinion paper focuses on these different aspects and places emphasis on the recovery of the placenta to diagnose congenital toxoplasmosis. What is the role of the placenta in T. gondii transmission and pathophysiology? T. gondii can invade and multiply within trophoblast cells [3], but the mechanisms by which this otherwise effective barrier can fail to protect the foetus, allowing some patho- gens to enter, remain unclear although some hypotheses have been suggested. Whereas an efficient immune re- sponse against Toxoplasma requires a T helper (Th)-1 cytokine pathway response involving interferon g (IFN- g) [4,5], the placental microenvironment is rich in inter- leukin 10 (IL-10) and promotes a Th-2 immune response to ensure maternal–foetal tolerance [1], which could facilitate infection of placental tissue [6]. The interplay between immune effectors of successful pregnancy and of anti-in- fectious response has been extensively described elsewhere [1,7]. The pivotal cytokine in this complex process is IFN-g, as shown in a mouse model where IFN-g synthesis follow- ing T. gondii infection led to abortion in pregnant wild type mice, but not in pregnant IFN-g knockout (KO) mice [8]. Such a deleterious effect of IFN-g is also described in pre- eclampsia in humans [9]. Thus, a delicate balance exists between the anti-T. gondii effector functions of IFN-g and its abortogenic effects, and both maternal and foetal environments contribute to this complex equilibrium (Figure 1) [10]. However, the role of IFN-g could be more ambiguous, as it was shown in vitro that it upregulates the expression of intercellular adhesion molecule (ICAM)-1 adhesin at the trophoblast cell surface and thereby con- tributes to enhanced adhesion of infected monocytes [11]. In addition, ICAM-1 is induced during placentitis [12] and could directly support transepithelial migration of the Opinion Corresponding author: Robert-Gangneux, F. (florence.robert-gangneux@univ-rennes1.fr) 530 1471-4922/$ – see front matter ß 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.pt.2011.09.005 Trends in Parasitology, December 2011, Vol. 27, No. 12