Abstract
Immune adaptation is a critical component of successful pregnancy. Of primary importance is the modification of cytokine production upon immune activation. With the discovery that normal pregnancy itself is a pro-inflammatory state, it was recognised that the classical Th1/Th2 cytokine paradigm, with a shift towards ‘type 2’ cytokine production (important for antibody production), and away from ‘type 1’ immunity (associated with cell mediated immunity and graft rejection), is too simplistic. It is now generally agreed that both arms of cytokine immunity are activated, but with a bias towards ‘type 2’ immunity. Many factors are released from the placenta that can influence the maternal cytokine balance. Here we focus on syncytiotrophoblast microvesicles (STBM) which are shed from the placenta into the maternal circulation. We show that STBM can bind to monocytes and B cells and induce cytokine release (TNFα, MIP-1α, IL-1α, IL-1β, IL-6, IL-8). Other cytokines are down-modulated, such as IP-10 which is associated with ‘type 1’ immunity. Therefore STBM may aid the ‘type 2’ skewed nature of normal pregnancy. We also observed that PBMC from third trimester normal pregnant women produce more TNFα and IL-6 in response to STBM than PBMC from non-pregnant women, confirming that maternal immune cells are primed by pregnancy, possibly through their interaction with STBM.
Highlights
A pregnant woman’s immune system is carefully controlled and adapted to accommodate the developing semi-allogenic fetus
peripheral blood mononuclear cells (PBMC) from a non pregnant woman were incubated with 50 mg/ml mechanically derived STBM (mSTBM), pSTBM or explant derived STBM (eSTBM) for 20 hours at 37uC, and supernatants used for cytokine array analysis, figure 1A. 36 cytokines were analysed and the array is not quantitative the plots obtained indicate the trends of cytokine production
As pSTBM and eSTBM induced a similar profile of cytokine production, we chose to use pSTBM in further experiments as only this method of preparation gives the high yield of microvesicles required for the study. mSTBM were included as a negative control
Summary
A pregnant woman’s immune system is carefully controlled and adapted to accommodate the developing semi-allogenic fetus. The adaptation can be seen by studying maternal cytokine responses to antigens throughout pregnancy. A bias towards type 2 immunity was proposed to prevent cell mediated rejection of the fetus [1], and such changes in cytokine immunity can be observed. Often during pregnancy classical type 1 syndromes alleviate, whereas type 2 syndromes worsen. Over recent years this concept has been shown to be too simplistic [2,3] and the inflammatory nature of normal pregnancy has become more apparent [4]. It is generally agreed that both arms of cytokine immunity are activated, but with a bias towards ‘type 2’ immunity [5]
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