Frontiers in Microbiology (Oct 2021)

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

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

DOI
https://doi.org/10.3389/fmicb.2021.741104
Journal volume & issue
Vol. 12

Abstract

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Infection with Toxoplasma gondii 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 T. gondii infection during pregnancy is unknown. In this study, we investigated the role of TLR2 in congenital toxoplasmosis using TLR2-deficient (TLR2−/−) mice. T. gondii infection on gestational day 12.5 (Gd12.5) induced more abnormal pregnancy, including premature birth and stillbirth, in wild-type mice than in TLR2−/− 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−/− mice. However, T. gondii 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−/− mice showed no changes in the expression of these cytokines, including IL-6 and tumor necrosis factor α, in response to T. gondii infection. Serum interferon-γ levels were significantly lower in the infected TLR2−/− mice than in the infected wild-type mice on Gd18.5. Thus, the TLR2−/− mice were less susceptible to the induction of immune responses by T. gondii infection during late pregnancy. Therefore, TLR2 signaling may play a role in the development of disease states during pregnancy, specifically placental hypofunction.

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