Impaired decidual macrophage efferocytosis of trophoblasts in preeclampsia

Objectives: Preeclampsia (PET) is associated with defective trophoblast invasion, with elevated numbers of apoptotic trophoblasts observed. Decidual macrophages (DM_φ) are thought to be key in removal of these cells via efferocytosis, which drives macrophages into an anti-inflammatory, tolerogenic phenotype. However, in PET DM_φ appear more pro-inflammatory which may affect their ability to efferocytose. This study investigated whether ex vivo DM_φ efferocytosis of trophoblasts is altered in preeclampsia.

Methods: Placentas were collected from healthy pregnancies (healthy controls HC, >37 weeks gestation, n=7-11), and pregnancies diagnosed with PET (30-37 weeks gestation, n=6-7). Decidua basalis macrophages (DBM_φ ) and decidua paritelais macrophages (DPM_φ ) were isolated and underwent phenotyping by flow cytometry. For efferocytosis, DM_φ were co-cultured with apoptotic BeWo trophoblasts labelled with cell tracker green, for 90 minutes, and uptake measured by flow cytometry. Co-currently, phagocytosis of fluorescently labelled Streptococcus agalactiae for 4 hours was measured by flow cytometry

Results: PET DBM_φ efferocytose significantly less apoptotic trophoblasts compared to HC (29±9% vs 61±9%, p<0.05). PET DBM_φ also phagocytose significantly less S. agalactiae compared to HC DBM_φ (10±3% vs 24±4%, p<0.05). Similarly, efferocytosis by PET DPM_φ was significantly reduced compared to HC (39±10% vs 60±10%, p<0.05), and phagocytosis by PET DPM_φ was significantly reduced compared to HC (10±2% vs 29±8%, p<0.05). There was no significant difference in phenotypic receptor expression between patient groups for either DM _φtype.

Conclusion: Our study is the first to demonstrate efferocytic function of ex vivo DM_φ , and demonstrates that in PET, DM_φ have impaired ability to both efferocytose apoptotic trophoblasts and phagocytose bacteria. Impaired DM_φ function in PET may lead to elevated trophoblast necrosis in the placenta, driving inflammation. Further understanding the effect of pregnancy complications on DM_φ function is vital to increase our understanding of the pathogensis of these conditions and identify novel immunomodulatory treatments.