The imbalance of the Th17/Treg axis following equine ascending placental infection.

This research article investigates how equine ascending placental infection influences the balance of Th17/Treg axis, indicating an increased Th17 response and decreased Treg response following this infection which may contribute to fatal outcomes like abortion or preterm labor in horses.

Research Context and Methodology

• The research focuses on ascending placentitis, a major cause of abortion in horses. The study aims to understand the adaptive immune response to this disease which has previously remained relatively unexplored.
• Sub-acute placentitis was experimentally induced in horses by way of trans-cervical inoculation of S. zooepidemicus, a bacterium that commonly causes injury in animals. The tissue samples of the endometrium and chorioallantois (membranes involved in pregnancy) were collected eight days after the inoculation.
• The researchers then assessed the expression of transcripts or gene expressions relating to four T helper cells (Th) types: Th1, Th2, Th17, and Tregs using RNA Sequencing. Immunohistochemistry (IHC) was also utilised to examine the transcription factors (proteins involved in gene expression) relating to each subtype in the tissues.
• Circulating cytokines, small proteins important in cell signaling, relating to Th1 (IFNg, IL-2), Th2 (IL-4, IL-5), Th17 (IL-17, IL-6), and Treg (IL-10, GM-CSF) were assessed using an immunoassay, a procedure for detecting or measuring specific proteins or other substances through their properties as antigens or antibodies.

Key Research Findings

• The study found an increase in Th1 and Th17-related transcripts in the chorioallantois following the infection, but no alterations were observed in the endometrium.
• The expression of Th2 and Treg-related transcripts was found to be dysregulated – their expressions increased for some transcripts while decreasing for others.
• Increase in Th1, Th2, and Th17 cell localisation in the diseased chorioallantois was noted. However, no Treg cells were observed in the diseased tissue.
• The researchers also noted an increase in secreted cytokines relating to Th1, Th2, Th17, and Treg populations in the maternal circulation eight days after inoculation.

Research Conclusions and Implications

• The research concludes that the Th1/Th17 response to ascending placentitis primarily occurs in the chorioallantois which suggests that the adaptive immune response happens mostly in the fetal-derived placental tissue.
• This study implies that ascending placentitis leads to an increase in Th cell populations (Th1, Th17, and Th2), while the Treg response decreases. This suggests that the S. zooepidemicus infection and consequent disease in horses are associated with an imbalance in the Th17/Treg axis.
• This imbalance, characterized by an increase in Th17-related responses and a decrease in Treg-related responses, could contribute to serious consequences such as fetal demise, abortion, or preterm labor in horses. More research is needed to substantiate these findings and understand the mechanisms at play.