Differential Distribution and Phenotype of Decidual Macrophages in Preeclamptic versus Control Pregnancies

Abstract

Maternal immune tolerance of the semiallogeneic fetus is a complex phenomenon. Macrophages are an abundant cell population in the human decidua, and changes in distribution or phenotype may be involved in the development of preeclampsia. The aim of this study was to assess the distribution and phenotype of macrophages in preterm preeclamptic, preterm control, and term control placentas. Placentas of preterm preeclamptic (n ‫؍‬ 6), preterm control (n ‫؍‬ 5), and term control pregnancies (n ‫؍‬ 6) were sequentially immunohistochemically stained for CD14, CD163, DC SIGN, and IL-10. The distributions of CD14 CD14 and CD163 expression increased significantly in preterm preeclamptic decidua basalis compared with preterm control pregnancies (P ‫؍‬ 0.0006 and P ‫؍‬ 0.034, respectively). IL-10 expression was significantly lower in the decidua parietalis of preterm preeclamptic pregnancies compared with preterm control pregnancies (P ‫؍‬ 0.03). The CD163/CD14 ratio was significantly lower in the decidua basalis (P ‫؍‬ 0.0293) and the DC SIGN/CD14 ratio was significantly higher in the decidua basalis (P < 0.0001) and parietalis (P < 0.0001) of preterm preeclamptic pregnancies compared with preterm control pregnancies. CD14 ؉ macrophages did express Flt-1. Alterations in distribution and phenotype of macrophages in the decidua of preterm preeclamptic pregnancies compared with control pregnancies may contribute to the pathogenesis of preeclampsia. (Am J

A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

“…All cases of pre-eclampsia (20/20) were infected with a high-risk HPV type. Our findings support the proposal that HPV infection contributes to the pathogenesis of pre-eclampsia, [37][38][39] and alters overall inflammatory marker expression in pregnancy. 40,41 In a cell culture setting, HPV infection impairs trophoblast cell function by inducing trophoblast cell death and defective endometrial cell recognition.…”

Immunological role of vitamin D at the maternal–fetal interface

“…M2 macrophage numbers in relation to total macrophages (CD163/CD14 ratio) were lower in placentas from preterm PET pregnancies compared with those from preterm 'controls'. Interestingly, total macrophage numbers were significantly higher in the PET group and positively correlated with PET severity (Schonkeren et al 2011). However, although this shift towards a pro-inflammatory cytokine environment is described in the context of malplacentation disorders, this is an over-simplification; contradictory information exists as outlined later in this review.…”

“…In the context of adverse pregnancy, elevated serum concentrations of IL12 (which augment the production of inflammatory cytokines) have also been measured in the peripheral blood of women with pre-eclampsia (PET) (Saito et al 1999). Lower levels of anti-inflammatory IL10 have also been reported in the decidua basalis in cases of PET (Schonkeren et al 2011, Darby et al 2013. Polarisation towards an M2 macrophage subtype has also been observed in normal-term placentas relative to those from women with pregnancies complicated by both preterm birth and PET.…”

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

“…Most studies have focused on the number of decidual macrophages and these have failed to show consistent results for instance showing both unaltered, decreased and increased numbers of macrophages in preeclamptic patients (Burk et al, 2001;Lockwood et al, 2006;Kim et al, 2007;Schonkeren et al, 2011). Thus, the role of decidual macrophages in the development of complications is likely to be more related to the function of macrophages (or a combination of the both).…”

“…Thus, the role of decidual macrophages in the development of complications is likely to be more related to the function of macrophages (or a combination of the both). Indeed, some studies have reported altered expression of M2 macrophage markers (for instance CD163, CD206 and CD209) (Schonkeren et al, 2011;Hsu et al, 2012;Prins et al, 2012) or production of factors influencing macrophage polarization (for instance GM-CSF and IL-10) (Hennessy et al, 1999;Huang et al, 2010;Schonkeren et al, 2011) in pregnancy complications. However, evidence is still scarce, partly reflecting the limited information about decidual macrophage function during healthy pregnancy.…”