T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells.

TLDR

Maternal immune responses affect fetal survival, with Th1 cytokines such as IFN‑γ and IL‑2 linked to fetal loss and Th2 cytokine IL‑10 protective, yet in leishmaniasis resistance is associated with a Th1 response while a Th2 response worsens disease. The study examined whether the protective Th1 response against Leishmania major in resistant C57BL/6 mice compromises concurrent pregnancy. In infected C57BL/6 mice, pregnancy failure increased, with more resorptions and pre‑implantation losses linked to higher IFN‑γ and TNF and lower IL‑4/IL‑10, whereas BALB/c mice were unaffected, indicating that a protective Th1 response can harm pregnancy.

Abstract

Maternal immune responses can influence fetal survival and several cytokines have harmful or protective effects on pregnancy. The Th1 cytokines IFN-gamma and IL-2 can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However, infections such as leishmaniasis show the opposite pattern: resistance is associated with the preferential mounting of a Th1 response, whereas a Th2 response exacerbates the disease. We therefore asked whether the curative Th1 response against Leishmania major in genetically resistant C57BL/6 mice, would compromise concurrent pregnancy. The number of resorptions as assessed by uterine scars was significantly increased in infected C57BL/6 mice and this was associated with a decreased production by placental cells of the Th2 cytokines IL-4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the frequency of pregnancy failure before implantation in C57BL/6 mice was also substantially increased. In contrast to C57BL/6 mice, early infection did not reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and succumb to infection. For both resorptions and implantations, there appeared to be a short period early in infection that was detrimental to pregnancy, followed by a period with lesser effects, and a later period that again induced higher resorptions or pre-implantation losses. These results suggest that a beneficial anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore, Th1 cytokines may be deleterious for not only placental maintenance but also preimplantation events.