Abstract
Placental immune responses are highly regulated to strike a balance between protection and tolerance. For relatively mild infections, protection encompasses both the mother and fetus; however, during worsening conditions, protection becomes exclusively reserved for the mother. Previously, we and others have shown that the host factor Perforin-2 plays a central role in protecting mice and cells against infection. Here, we analyzed Perforin-2 activity in the mouse placenta to determine whether Perforin-2 plays a similarly protective role. We show that Perforin-2 is critical for inhibiting Listeria monocytogenes colonization of the placenta and fetus and that this protection is due to both maternal and fetal-encoded Perforin-2. Perforin-2 mRNA is readily detectable in individual immune cells of the decidua and these levels are further enhanced specifically in decidual macrophages during high-dose infections that result in fetal expulsion. Unexpectedly, inductive Perforin-2 expression in decidual macrophages did not occur during milder infections in which fetal viability remained intact. This pattern of expression significantly differed from that observed in splenic macrophages in which inductive Perforin-2 expression was observed in both high and mild infection conditions. In the placenta, inductive Perforin-2 expression in decidual macrophages was co-incident with their polarization from a M2 to M1 phenotype that normally occurs in the placenta during high-burden infections. Our results suggest that Perforin-2 is part of a host response that is protective either for both the mother and fetus in milder infections or exclusively for the mother during high-dose infections.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
PG and KS conceived the project, designed the experiments, and interpreted the data. All experiments and data collection were performed by PG with assistance by VM, RH, MW, RCC, KLN, MA, and KS. Contributions to the development of methodologies were made by LP and NS. The manuscript was primarily written by PG with assistance by KS.