Disturbances in placental immunology: ready for therapeutic interventions?

Abstract

Recent studies have provided new insight into aberrations in the immunological interplay between mother and fetus and their potential role in the development of recurrent fetal loss and preeclampsia. The action of anti-phospholipid antibodies in recurrent fetal loss is now proposed to involve the complement system, neutrophil activation and the production of TNFα by immune bystander cells. A clear involvement of the immune system is emerging in preeclampsia, involving mainly the innate arm, especially neutrophils. The activation of peripheral neutrophils by placentally released inflammatory debris triggers the induction of neutrophil extracellular traps (NETs), which may lead to an occlusion of the intervillous space, thereby further promoting a condition of placental hypoxia. It has, hence, been suggested that new therapeutic strategies be developed, including the possible use of TNFα antagonists in cases of recurrent miscarriage. These strategies need to be addressed with caution due to the possible induction of fetal congenital abnormalities.

Ultrastructural characterization of cystic fibrosis sputum using atomic force and scanning electron microscopy

“…These findings, together with the immense quantities of NETs found in CF airways, suggest that the NET production observed in the examined CF patients was inadequately high related to the bacterial challenge present in its microenvironment. NET overproduction, which might lead to tissue damage, has been reported in other inflammatory disease conditions, such as preeclampsia [22][23][24][25] periodontitis [26,27], autoimmune smallvessel vasculitis [28] and others. Impaired NET degradation has been reported in lupus [29].…”

Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms?

“…While the adaptive immune response is down-modulated during pregnancy, the innate immune response is enhanced: the number of PMN increases and PMN undergo functional and metabolic changes [57][58][59][60]. Pregnancy-induced inflammatory changes in peripheral PMN are akin to those of sepsis [61], and there is evidence for PMN activation by syncytiotrophoblast-derived microparticles [62][63][64]. Delayed apoptosis of neutrophils in normal pregnancy allows inflammation to persist and may explain pregnancy-associated neutrophilia.…”

Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats

“…PE is associated with decreased fetal development and increased risk of future maternal heart disease. Although recent scientific findings have greatly aided in explaining the potential mechanisms involved in the development of PE, the exact causes remain unknown and effective treatments for PE remain elusive.Abnormal maternal immune system responses play a key role in the development of PE (10,13,31). A current theory is that women who develop PE have abnormal immunological responses to the fetus and placenta and that the hypertension and proteinuria represent clinical signs of a mild form of fetal rejection, while severe forms of PE result in spontaneous abortion and fetal demise.…”