Altered Glycosylation Contributes to Placental Dysfunction Upon Early Disruption of the NK Cell-DC Dynamics

Immune cells [e. g., dendritic cells (DC) and natural killer (NK) cells] are critical players during the pre-placentation stage for successful mammalian pregnancy. Proper placental and fetal development relies on balanced DC-NK cell interactions regulating immune cell homing, maternal vascular expansion, and trophoblast functions. Previously, we showed thatin vivodisruption of the uterine NK cell-DC balance interferes with the decidualization process, with subsequent impact on placental and fetal development leading to fetal growth restriction. Glycans are essential determinants of reproductive health and the glycocode expressed in a particular compartment (e.g., placenta) is highly dependent on the cell type and its developmental and pathological state. Here, we aimed to investigate the maternal and placental glycovariation during the pre- and post-placentation period associated with disruption of the NK cell-DC dynamics during early pregnancy. We observed that depletion of NK cells was associated with significant increases of O- and N-linked glycosylation and sialylation in the decidual vascular zone during the pre-placental period, followed by downregulation of core 1 and poly-LacNAc extended O-glycans and increased expression of branched N-glycans affecting mainly the placental giant cells and spongiotrophoblasts of the junctional zone. On the other hand, expansion of DC induced a milder increase of Tn antigen (truncated form of mucin-type O-glycans) and branched N-glycan expression in the vascular zone, with only modest changes in the glycosylation pattern during the post-placentation period. In both groups, this spatiotemporal variation in the glycosylation pattern of the implantation site was accompanied by corresponding changes in galectin-1 expression. Our results show that pre- and post- placentation implantation sites have a differential glycopattern upon disruption of the NK cell-DC dynamics, suggesting that immune imbalance early in gestation impacts placentation and fetal development by directly influencing the placental glycocode

NK cell-derived IL-10 is critical for DC-NK cell dialogue at the maternal- fetal interface

DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion. Remarkably, DC expansion in IL-10−/− dams provoked pregnancy loss, which could be abrogated by the adoptive transfer of IL-10+/+ NK cells and not by IL-10−/− NK cells. Furthermore, the IL-10 expressing NK cells markedly enhanced angiogenic responses and placental development in DC expanded IL-10−/− dams. Thus, the capacity of NK cells to secrete IL-10 plays a unique role facilitating the DC- NK cell dialogue during the establishment of a healthy gestation

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy

Disruption of fetal-maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin-9 (LGALS9), a tandem repeat lectin associated with immune modulation, is expressed in the endometrium during the mid and late secretory phases and in decidua during human early pregnancy. However, the role of LGALS9 during pregnancy remains poorly understood. We used real-time PCR and immunohistochemical staining to analyze the expression of Lgals9/LGALS9 during mouse gestation as well as in human tissues obtained from normal pregnancy and spontaneous abortions. In mice, three Lgals9 splice variants were detected, the expression of which was differentially regulated during gestation. Furthermore, decidual Lgals9 expression was deregulated in a mouse model of spontaneous abortion, whereas placental levels did not change. We further found that the LGALS9 D5 isoform suppresses interferon gamma production by decidual natural killer cells. In human patients, six Lgals9 splice variants were detected, and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these results show a differential regulation of Lgals9 isoform expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes.Fil: Heusschen, Roy. VU University Medical Center; Países BajosFil: Freitag, Nancy. Medicine University of Berlin; AlemaniaFil: Tirado González, Irene. Medicine University of Berlin; AlemaniaFil: Barrientos, Gabriela Laura. Medicine University of Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moschansky, Petra. Medicine University of Berlin; AlemaniaFil: Muñoz Fernández, Raquel. Consejo Superior de Investigaciones Cientificas; EspañaFil: Leno Durán, Ester. Universidad de Granada; EspañaFil: Klapp, Burghard F.. Medicine University of Berlin; AlemaniaFil: Thijssen, Victor L.J.L.. VU University Medical Center; Países BajosFil: Blois, Sandra M.. Medicine University of Berlin; Alemani

Differential immunoregulation in successful oocyte donation pregnancies compared with naturally conceived pregnancies

In oocyte donation (OD) pregnancies, there is a higher level of antigenic dissimilarity between mother and fetus compared with naturally conceived (NC) pregnancies. We hypothesize that a higher degree and/or a different type of immunoregulation is necessary to maintain an uncomplicated OD pregnancy. Different immunological aspects of successful OD pregnancies (n=28) were compared with those of NC pregnancies (n=51), and non-donor IVF (n=20) pregnancies. Maternal peripheral blood mononuclear cells (mPBMCs) were characterized by flow cytometry; the outcome correlated with the number of mother child HLA mismatches. The fetus-specific alloreactivity of mPBMCs was measured in a mixed lymphocyte reaction. The percentages of CD4(+)CD25(bright) and CD4(+)CD25(dim) cells were higher in mPBMCs of OD and IVF pregnancies compared with NC pregnancies. The percentage of CD4(+)CD25(dim) cells in mPBMCs of OD pregnancies correlated positively with the number of HLA mismatches. Functional studies showed a lower proliferative response to umbilical cord blood by mPBMCs in OD pregnancies. In conclusion, we found a higher degree of peripheral immunoregulation in OD and IVF pregnancies compared with NC pregnancies. A higher number of HLA mismatches in successful OD pregnancies leads to increased percentages of activated T cells in peripheral blood, but not to a higher alloreactivity to the fetus. These studies show that immunoregulation in OD pregnancy is different from that in NC pregnancies. The antigenic dissimilarity in OD pregnancies may play a role in the pathophysiology of preeclampsia. (C) 2013 Elsevier Ireland Ltd. All rights reserved