Toxoplasma gondii-induced foetal resorption in mice involves interferon-gamma-induced apoptosis and spiral artery dilation at the maternofoetal interface.
The severity of congenital toxoplasmosis depends on the stage of the pregnancy at which infection takes place. Infection during the first trimester generally leads to miscarriage, through an unknown mechanism. Toxoplasma gondii infection is normally controlled by a strong Th1-type response with IFN-gamma production. To investigate the mechanisms of foetal resorption induced by T. gondii, pregnant Swiss-Webster mice were infected 1 day post coïtum with the avirulent Me49 strain. Mated recipients were examined at mid-gestation. Few parasites and no cytolytic effects were detected 10 days post coïtum in implantation sites undergoing resorption. Resorption was accompanied by haemorrhage, spiral artery dilation, hypocellularity of the decidua basalis, apoptosis of placental cells, a decline in uterine mature natural killer cell numbers, increased indoleamine 2,3-dioxygenase mRNA levels and reduced IL-15 mRNA levels. Given the role of IFN-gammaR(-/-) in non-infectious abortive processes, IFN-gammaR(-/-) mice were used to investigate its local role in T. gondii-induced foetal resorption. IFN-gammaR(-/-) mice showed 50% less foetal resorption than their wild-type counterparts, and spiral artery dilation and placental cell apoptosis were both abolished. These results strongly suggest that, at least in mice, T. gondii-induced abortion in early gestation is not due to a direct action of the parasite at the maternofoetal interface but rather to massive IFN-gamma release.
Institut de Parasitologie et de Pathologie Tropicale, UPRES-EA 3950, Université Louis Pasteur, Strasbourg F-67000, France.
A
A
Senegas
O
O
Villard
A
A
Neuville
L
L
Marcellin
A W
AW
Pfaff
T
T
Steinmetz
M
M
Mousli
J P
JP
Klein
E
E
Candolfi
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005327:Fetal Resorption / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis*; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D010920:Placenta / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D011247:Pregnancy / Q000276:immunology; D015597:Pregnancy Complications, Parasitic / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D017471:Receptors, Interferon; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000473:pathology; D014599:Uterus / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000096743:Interferon gamma Receptor
D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor