title: Toxoplasma gondii regulates ICAM-1 mediated monocyte adhesion to trophoblasts.
abstract: Materno-foetal transmission causes one of the most serious forms of infection with the intracellular protozoan parasite Toxoplasma gondii. In the placenta, trophoblast cells constitute the barrier between maternal circulation and foetal tissue. We looked at the factors that determine the extent of cell adhesion to human BeWo trophoblast cells during T. gondii infection. BeWo monolayers stimulated with the supernatant of T. gondii-infected PBMC showed a large increase in THP-1 cell adhesion and upregulation of the intercellular adhesion molecule (ICAM)-1. Neutralization of cytokines by corresponding antibodies demonstrated that anti-IFN-gamma, but not anti-TNF-alpha or anti-IL-1beta, led to a significant reduction of THP-1 adhesion to a BeWo monolayer. Treatment of BeWo cells with single cytokines failed to induce upregulation of adhesion. In contrast, simultaneous treatment with IFN-gamma and either TNF-alpha or IL-1beta mimicked strongly the effect of infected cell supernatant. The results suggest that IFN-gamma plays a pivotal role in the cell adhesion process through upregulation of ICAM-1 and in the process of congenital transmission of T. gondii.
authors.affiliation: Cellular and Molecular Physiopathology and Infection Laboratory, Inserm UMR-S 392, Parasitology and Tropical Pathology Institute, Faculty of Medicine, Louis Pasteur University, Strasbourg, France. alexander.pfaff@medecine.u-strasbg.fr
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Pfaff
authors.forename: Sophie
authors.initials: S
authors.lastname: Georges
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abou-Bacar
authors.forename: Valerie
authors.initials: V
authors.lastname: Letscher-Bru
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Klein
authors.forename: Marc
authors.initials: M
authors.lastname: Mousli
authors.forename: Ermanno
authors.initials: E
authors.lastname: Candolfi
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D016207:Cytokines / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D011247:Pregnancy; D014122:Toxoplasma / Q000502:physiology*; D014123:Toxoplasmosis / Q000378:metabolism* / Q000635:transmission; D014327:Trophoblasts / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1