Abstract
Macrophages at the maternal-placental interface coordinate opposite demands under the control of trophoblast cells such as the response against pathogens on one hand, and apoptotic cell clearance and wound healing with the production of suppressor cytokines. Here, we investigated whether trophoblast cells induce maternal monocyte activation towards an alternative activated macrophage profile and whether bacterial or viral stimuli modulate their migratory properties. We used an in vitro model of the maternal-placental interface represented by co-cultures of CD14+ cells isolated from fertile women with first trimester trophoblast cell line (Swan-71 cells) in the presence or absence of pathogen associated molecular pattern (PAMP) stimuli lipopolysaccharide (LPS), peptidoglycan (PGN) or poly [I:C]). Maternal CD14+ cells showed increased CD16 and CD39 expression, both markers associated to an alternative activation profile, with no changes in CD80 expression after trophoblast cell interaction. These changes were accompanied by increased IL-10 and decreased IL-12 production by CD14+ cells. After stimulation with LPS, PGN or poly [I:C], monocytes co-cultured with trophoblast cells had lower production of TNF-α and IL-1β compared with non co-cultured monocytes. Interestingly, monocyte migration towards trophoblast cells was prevented in the presence of LPS or PGN but not after 24h of stimulation with poly [I:C]. LPS or PGN also decreased CCR5, CXCL-8 and CCL5 expression. Finally, trophoblast cells co-cultured with monocytes in the presence of pathological stimuli failed to increase chemokine expression, indicating a bidirectional effect. In conclusion, trophoblast might ‘instruct’ maternal monocytes to express an alternative activation profile and restrain their early recruitment under pathological threats as one of the first strategies to avoid potential tissue damage at the maternal-placental interface.
Highlights
The control of immune homeostasis at the maternal-placental interface involves several and redundant immunoregulatory circuits
On the basis that trophoblast cells contribute to maternal monocyte differentiation to macrophage alternative activation profiles, we hypothesized that trophoblasts under pathogen stimulation modulate chemokine networks that act on monocytes/macrophages as a strategy to avoid potential tissue damage and pregnancy loss
CD16 is the FccRIII, a marker associated with a regulatory macrophage profile [14] and CD39 is a surface enzyme that was proposed as self-limiting for macrophage pro-inflammatory activation based in its rapid catabolism of endogenous adenosine triphosphate (ATP) into adenosine [24]
Summary
The control of immune homeostasis at the maternal-placental interface involves several and redundant immunoregulatory circuits. Macrophages can express a classical inflammatory profile to control the risk of infection by ascending or blood-borne pathogens [13] In this sense, evidence indicates that macrophage functional profiles are determined by the kind of stimulus and the specific micro-environmental conditions in which cells were differentiated prior to their activation [14,15]. On the basis that trophoblast cells contribute to maternal monocyte differentiation to macrophage alternative activation profiles, we hypothesized that trophoblasts under pathogen stimulation modulate chemokine networks that act on monocytes/macrophages as a strategy to avoid potential tissue damage and pregnancy loss. We showed that trophoblast cells, in the presence of stimuli mimicking bacterial or viral infections, differentially induce the activation of maternal monocytes to alternative activated macrophage profile and modulated chemokine and chemokine-receptor expression affecting their migratory properties
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
