M1/M2 Macrophage Polarity in Normal and Complicated Pregnancy

Brown, Mary Bomberger; Chamier, Maria von; Allam, Ayman B.; Reyes, Leticia

doi:10.3389/fimmu.2014.00606

Cited by 183 publications

(196 citation statements)

References 113 publications

(194 reference statements)

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“…IL10, among other factors, can induce M2 antiinflammatory macrophage polarization, which promotes tissue remodeling and immune tolerance (35). In the IL11-treated mouse placenta, IL10 was significantly down-regulated, suggesting that IL11 may promote M2 macrophage polarization.…”

Section: Discussionmentioning

confidence: 94%

Interleukin-11 alters placentation and causes preeclampsia features in mice

Winship

Koga

Menkhorst

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal-fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE.placenta | trophoblast | cytokines | pregnancy P reeclampsia (PE) is a pregnancy-induced disorder characterized by hypertension and proteinuria, unique to humans, affecting ∼8% of pregnancies (1). The etiology is poorly understood (2); nevertheless, there is substantial evidence showing abnormal placentation is the key underlying cause. During pregnancy, highly invasive extravillous trophoblasts (EVT) acquire vascular-like properties to remodel uterine spiral arterioles. This creates low-resistance, large-diameter vessels that promote uteroplacental blood supply to sustain fetal growth (3, 4). It is widely accepted that inadequate trophoblast invasion and impaired uterine spiral artery remodeling is an initiating factor in the development of PE (5). This is thought to impair uteroplacental arterial flow and lead to placental oxidative stress (6). PE is associated with increased placental secretion of proinflammatory cytokines (7) and angiogenic regulators (8), thought to contribute to widespread maternal endothelial dysfunction. The clinical symptoms of PE are hypertension, proteinuria, and peripheral and/or cerebral edema. Symptoms can differentially manifest during the second (early-onset, EO), or third (late-onset, LO) trimester (9). In addition to the maternal symptoms, PE is also frequently associated with prematurit...

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Section: Discussionmentioning

confidence: 94%

Interleukin-11 alters placentation and causes preeclampsia features in mice

Winship

Koga

Menkhorst

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…and the other more pro-inflammatory [67]. P. gingivalis infection resulted in a notable decrease in CD206 + dMΦs ( Figure 5).…”

Section: P Gingivalis As a Vascular Pathogen Of The Placental Bedmentioning

confidence: 99%

“…Decidual macrophage (dMΦ) populations are heterogeneous, but most tend towards M2 polarity phenotypes (M2a, M2b, and M2c) based on their expression of IL-10, TGF-β, indoleamine 2,3-dioxygenase (IDO), IL-6, and/or TNF-α [67], and their ability to suppress uNK cytotoxicity toward EVT [68]. dMΦ can minimize inflammation by phagocytosing cellular debris from apoptotic VSMC [67], but also have the capacity to revert to a pro-inflammatory phenotype, as seen in recurrent miscarriage, preeclampsia, and fetal growth restriction [67,69].…”

Section: Uterine Vascular Changes During Pregnancymentioning

confidence: 99%

Porphyromonas gingivalisand adverse pregnancy outcome

Reyes

Phillips

Wolfe

et al. 2017

Journal of Oral Microbiology

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Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium considered to be an important pathogen of periodontal disease that is also implicated in adverse pregnancy outcome (APO). Until recently, our understanding of the role of P. gingivalis in APO has been limited and sometimes contradictory. The purpose of this review is to provide an overview of past and current research on P. gingivalis that addresses some of the controversies concerning the role of this organism in the pathogenesis of APO.ARTICLE HISTORY

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“…Pathogens then seize on this opportunity to cross from the maternal tissues/blood into fetal circulation. Because many flaviviruses replicate in macrophages, and infection can be enhanced via Fcg receptors [28], it should also be mentioned that the villous stroma contains fetal M2 macrophages (Hofbauer cells) expressing numerous Fcg receptors [29], and syncytiotrophoblasts express neonatal Fc receptors (FcRn) [30]. The latter facilitate passive immunization of the fetus by allowing transcytosis of immunoglobulin G (IgG) across the syncytium.…”

Section: Placentamentioning

confidence: 98%

Neuroteratogenic Viruses and Lessons for Zika Virus Models

Kim

Shresta

2016

Trends in Microbiology

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The Centers for Disease Control and Prevention has confirmed that Zika virus (ZIKV) causes congenital microcephaly. ZIKV now joins five other neuroteratogenic (NT) viruses in humans and ZIKV research is in its infancy. In addition, there is only one other NT human arbovirus (Venezuelan equine encephalitis virus), which is also poorly understood. But further insight into ZIKV can be found by evaluating arboviruses in domestic animals, of which there are at least seven NT viruses, three of which have been well studied. Here we review two key anatomical structures involved in modeling transplacental NT virus transmission: the placenta and the fetal blood-brain barrier. We then survey major research findings regarding transmission of NT viruses for guidance in establishing a mouse model of Zika disease that is crucial for a better understanding of ZIKV transmission and pathogenesis.

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M1/M2 Macrophage Polarity in Normal and Complicated Pregnancy

Cited by 183 publications

References 113 publications

Interleukin-11 alters placentation and causes preeclampsia features in mice

Interleukin-11 alters placentation and causes preeclampsia features in mice

Porphyromonas gingivalisand adverse pregnancy outcome

Neuroteratogenic Viruses and Lessons for Zika Virus Models

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