In addition to interferon, the trophoblast has an ability to produce anti-microbial factors such as secretory leukocyte protease inhibitor (SLPI), 2′, 5′-oligoadenylate synthetase (OAS), Myxovirus resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G(APOBEC3G). These all have a direct effect on viral activity.47 These findings suggested

that the placenta and especially trophoblasts function as an active barrier preventing the transmission of certain viral infections to the fetus.38,50 In summary, all these studies suggest that trophoblasts APO866 are able to recognize bacterial or viral products through TLRs and induce differential responses (Fig. 2). The factor(s) associated with the type of response may determine the final outcome and be associated with pregnancy disorders such as preterm

labor, pre-eclampsia or IUGR. Recently, we proposed that trophoblast cells are potentially able to modulate the immune system at the maternal–fetal interface, by regulating various immune cell functions.38 Our earlier studies demonstrated that first-trimester trophoblasts constitutively secrete cytokines/chemokines Veliparib order such as, GRO-α, MCP-1 and IL8; and that these trophoblasts are also able to recruit monocytes/macrophages, NK cells and neutrophils.38,51 This cytokine/chemokine expression in trophoblasts is further enhanced upon ligation by TLR4 or TLR3 agonists, followed by a significant Orotic acid increase in the recruitment of immune cells.38 Moreover, the factors produced by trophoblasts have a potent modulatory effect on the maternal immune cells by determining their differentiation and state of activation. For example, monocytes/macrophages

incubated in the presence of trophoblasts or their condition media become less sensitive to LPS stimulation.51 Based on these observations, we propose that the trophoblast is able to ‘educate’ immune cells, where signals originated from trophoblast could determine the subsequent immune cell behavior. This proper trophoblast–immune cell cross-talk may be essential for a normal pregnancy, and changes or defects in this interaction may lead to pregnancy complications. The importance of TLR’s role in various pregnancy disorders, such as abortion, preterm labor, pre-eclampsia, and even fetal disorder has been demonstrated by either animal models or clinical observations. First, we will review studies of animal models followed by clinical studies. TLR-2 and TLR-4 response and preterm labor: It has been established that gram-negative bacteria trigger preterm labor in various animal models, and many attempts have been made to clarify this mechanism. Wang and Hirsch reported that TLR4 is essential for normal susceptibility to preterm delivery induced by gram-negative bacteria using TLR4 mutant mice model.