Abstract

BackgroundDuring pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response.MethodsWe compare culture-generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy.ResultsWe show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients.ConclusionsHere, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.

Highlights

  • During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus

  • In some cases the monocyte derived Dendritic cells (DCs) (MDDC) treated for 24 h with 10 ug/ml of E2 or PG were infected with New Castle Disease Virus NDV-B1 for 10 h at and MOI of 0.5. myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) were treated with each specific condition right after their isolation

  • Myeloid DCs and plasmacytoid secrete a-defensins 1-3 We have previously reported that a-defensins 1-3 levels were almost undetectable in monocytes but when differentiated into DCs (MDDCs) after 7 days in culture, they produce and secrete a-defensins 1-3 [4]

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Summary

Introduction

During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3 This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response. Upon exposure to microbial invaders, they undergo a maturational change characterized by the up-regulation of surface molecules involved in the interaction with T cells and the release of numerous cytokines This culminates in their migration to lymph nodes, where microbe-derived peptides are presented to specific T cells and initiation of the adaptive immune response occurs [11,12]. Other DC populations such as the plasmacytoid DCs (pDCs) have been proposed as important mediators of innate immunity because of their ability to produce large amounts of type I interferon (IFN) following viral infection

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