Selected aspects of the innate immune system in relation to preterm birth.

Abstract

The prevention of uterine infection is critical for appropriate fetal development and term delivery. One of the major defense mechanisms against infection is the innate immune system. Since preterm and term delivery are induced by inflammatory processes, preterm activation of the inflammatory cascades can induce preterm rupture of the membranes (PROM) and preterm delivery. In this review we will focus on some of the components of the innate immune system that are involved in the protection of the pregnant uterus from infection, but that may also have a function in PROM and preterm delivery. The family of Toll Like Receptors (TLRs) is a collection of receptors that are able to respond to a specific microbial component, so called pathogen-associated molecular patterns (PAMPs). They are important in the protection of the host to infectious agents. Natural antimicrobials are prominent in the (pregnant-) uterus. Evidence suggests that aberrant production of natural antimicrobials may cause preterm birth. The function of two groups of natural antimicrobials, lactoferrin and defensins, in the process of preterm birth will be discussed. Uterine Natural Killer (uNK) cells are abundantly present in the pregnant uterus. Upon activation they can induce the production of natural antimicrobials and pro-inflammatory cytokines. Evidence is increasing that uNK cells have a prominent role in the induction of preterm birth. The balance between immune activation to protect the uterus from infections and immune inhibition to prevent preterm birth is important. Increased knowledge of this delicate balance might help to find new approaches in the prevention of preterm birth.