AUTHOR=Ikeda Rina , Ushio Nanako , Abdou Ahmed M. , Furuoka Hidefumi , Nishikawa Yoshifumi 

TITLE=Toll-Like Receptor 2 is Involved in Abnormal Pregnancy in Mice Infected with Toxoplasma gondii During Late Pregnancy

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.741104

DOI=10.3389/fmicb.2021.741104

ISSN=1664-302X

ABSTRACT=<p>Infection with <italic>Toxoplasma gondii</italic> during pregnancy causes failure of pregnancy maintenance, resulting in fetal death, abortion, stillbirth, or premature birth, but the mechanism of disease onset remains unclear. Although Toll-like receptor 2 (TLR2) is expressed on antigen-presenting cells and trophoblasts, the role of TLR2 in <italic>T. gondii</italic> infection during pregnancy is unknown. In this study, we investigated the role of TLR2 in congenital toxoplasmosis using TLR2-deficient (TLR2<sup>−/−</sup>) mice. <italic>T. gondii</italic> infection on gestational day 12.5 (Gd12.5) induced more abnormal pregnancy, including premature birth and stillbirth, in wild-type mice than in TLR2<sup>−/−</sup> mice. Multiple calcifications were observed in the placentas of the infected wild-type mice. At Gd18.5 (6days postinfection), the parasite numbers in the placenta and uterus and the histological changes did not differ significantly between the wild-type and TLR2<sup>−/−</sup> mice. However, <italic>T. gondii</italic> infection reduced the mRNA expression of interleukin-12p40 (IL-12p40) and increased IL-4 and IL-10 mRNAs in the placentas of the wild-type mice. In contrast, the placentas of the TLR2<sup>−/−</sup> mice showed no changes in the expression of these cytokines, including IL-6 and tumor necrosis factor α, in response to <italic>T. gondii</italic> infection. Serum interferon-γ levels were significantly lower in the infected TLR2<sup>−/−</sup> mice than in the infected wild-type mice on Gd18.5. Thus, the TLR2<sup>−/−</sup> mice were less susceptible to the induction of immune responses by <italic>T. gondii</italic> infection during late pregnancy. Therefore, TLR2 signaling may play a role in the development of disease states during pregnancy, specifically placental hypofunction.</p>