Human gestation-associated tissues express functional cytosolic nucleic acid sensing pattern recognition receptors

Area of Science:

• Immunology
• Reproductive Biology
• Infectious Diseases

Background:

• Viral infections are increasingly linked to adverse pregnancy outcomes.
• Innate immune pattern recognition receptors (PRRs) and their cytokine signaling pathways are hypothesized to mediate infection's impact at the maternal-fetal interface.
• Understanding PRR function in gestation-associated tissues is crucial for identifying mechanisms of pregnancy complications.

Purpose of the Study:

• To investigate the expression and functional response of nucleic acid-sensing PRRs in human term gestation-associated tissues.
• To examine Toll-like receptors (TLR-3, -7, -8, -9) and RIG-I-like receptors (RIG-I, MDA5, LGP2) in placenta, choriodecidua, and amnion.
• To determine the cytokine (IL-6, IL-8) production in response to specific PRR agonists in an explant model.

Main Methods:

• Immunohistochemistry was used to detect PRR expression in human term placenta, choriodecidua, and amnion.
• An explant model was employed to assess functional responses to specific agonists for TLR-3, -7, -8, -9, and RIG-I/MDA5.
• Cytokine levels (IL-6, IL-8) were measured following stimulation.
• Hierarchical clustering analyzed differential tissue responses to nucleic acid ligands.

Main Results:

• PRRs (TLR-3, -7, -8, RIG-I/MDA5) were expressed in term gestation-associated tissues.
• Specific agonists significantly increased IL-6 and/or IL-8 production, except for the TLR-9 agonist.
• Placenta and choriodecidua showed similar IL-8 responses, while choriodecidua and amnion exhibited similar IL-6 responses.
• Differential tissue-specific responses to nucleic acid ligands were observed.

Conclusions:

• Human term gestation-associated tissues possess broad responsiveness via TLR-3, TLR-7, TLR-8, and RIG-1/MDA5.
• Differential cytokine production by tissue types suggests distinct roles in pregnancy outcomes.
• These findings highlight potential mechanisms linking viral infections and adverse obstetric outcomes.