Intercellular adhesion molecule (ICAM)-1 is required to control Toxoplasma gondii infection in uterine tissues and establish a successful gestation in a murine model of congenital toxoplasmosis.

The placenta acts as a critical barrier against pathogens during pregnancy, although Toxoplasma gondii can breach this defense, leading to congenital infections. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule involved in immune responses, including leukocyte recruitment and pathogen clearance. Here, we investigate the role of ICAM-1 in gestational success and T. gondii infection using wild-type (WT) and ICAM-1 knockout (ICAM-1-/-) mice across early, mid- and late pregnancy stages. In early pregnancy, ICAM-1-/- mice infected with T. gondii exhibited a significantly higher embryonic loss rate (63 %) compared to WT mice (5 %). This was accompanied by an increased parasite burden in uterine tissues and elevated systemic and local IFN-γ levels, despite a reduced local inflammatory response. In contrast, mid-pregnancy showed no significant differences in fetal loss or implantation success among groups, suggesting ICAM-1 plays a limited role at this stage. During late pregnancy, ICAM-1-/- mice experienced higher embryonic loss rates (40 %) compared to WT mice (26.2 %), along with reduced implantation success and elevated IFN-γ levels, though parasite burden remained unchanged. Histological analysis revealed a less severe inflammatory profile in infected ICAM-1-/- uterine tissues, marked by reduced necrosis and hyperemia compared to WT mice. FOXP3 expression, a marker of regulatory T cells, was unaffected by ICAM-1, although a trend towards reestablishment was observed in infected ICAM-1-/- mice. Our findings underscore the critical role of ICAM-1 in ensuring gestational success during T. gondii infection, particularly in early pregnancy, by modulating immune responses at the maternal-fetal interface.