The negative regulators of the host immune response: an unexplored pathway in preterm birth.

Abstract

Toll-like receptors (TLRs) are essential mediators of host immunity. TLR activation must be tightly regulated to prevent an exaggerated immune response from devastating the host. These studies assessed the expression of negative regulators (interleukin receptor-associated kinase [IRAK]-3, IRAK-1, Fas-associated protein with death domain) during pregnancy and in preterm birth (PTB). Tissues (uterine, cervix, placenta, and spleens) from the following experimental groups were harvested: (1) nonpregnant mice, (2) pregnant mice across gestation, (3) murine model of PTB, and (4) pregnant mice exposed to medroxyprogesterone acetate (MPA). Negative regulators are differentially expressed in the uterus during pregnancy. In the setting of PTB, IRAK-3 is significantly increased in the uterus and cervix but not the placenta. In maternal spleens, IRAK-3 and IRAK-1 are increased in response to intrauterine inflammation. MPA can increase IRAK expression in cervical tissues. Negative regulators of the maternal immune response may play an important role in protecting pregnancies from an exaggerated inflammatory response.