Potential role of macrophages as immunoregulators of pregnancy

Abstract

The role of the maternal immune system during pregnancy has focused mainly on the aspect of immune tolerance to the invading trophoblast and, therefore, fetus. While this is a critical aspect of reproductive immunology, it is also important to consider the function of the maternal immune system in the promotion of implantation and maintenance of pregnancy. Apoptosis or cell death is not the final stage in tissue development. The quick and effective removal of apoptotic cells by tissue macrophages represents a vital process preventing "leak" of self-antigens and promoting the production of proliferative/survival factors. One of the key requirements of apoptotic cell clearance is the resolution of inflammatory conditions, which, as in the case of pregnancy, may have lethal consequences. This review will focus on decidual macrophages and their role on apoptosis and cell clearance during pregnancy.

Figure 1

Effect of clearance of apoptotic cells by macrophages. A. Clearance of apoptotic cells induce the expression, by macrophages, of anti-inflammatory cytokines with protective effects on trophoblast survival and immunological tolerance. B. Changes in the cytokine milieu, owing to elevated levels of apoptotic bodies and inefficient clearance, will result in a pro-inflammatory microenvironment that in turn may result in changes in trophoblast resistance to Fas-mediated apoptosis and the maternal immune system

Figure 2

Differential Distribution of macrophages in normal pregnancy and pregnancy complicated with preeclamsia and IUGR. While in normal pregnancies macrophages are located in the stroma surrounding the transformed spiral arteries and extravillous trophoblast (A) ; in pre-eclampsia macrophages are located within and around the spiral arteries separating them from the trophoblast cells (B). In the normal condition, macrophages promote trophoblast survival; while in the pathologic state induce apoptosis

Figure 3

Macrophages phagocytose apoptotic first trimester trophoblasts. Apoptotic trophoblasts cells (green) are engulfed by THP-1-differentiated macrophages (red).

Figure 4

Phagocytosis of apoptotic cells by macrophages influences trophoblast apoptosis. Trophoblast cells were treated with macrophage condition media. Caspase 3 and XIAP expression was determined after 24 h incubation. NT: Control, CPT: Trophoblast cells treated with camptothecin. Low, High Med: Condition media from macrophages treated with either low, high and medium concentration of apoptotic cells.