Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL: A Potential Role for Macrophages in Trophoblast Apoptosis

Guenther, Sabine; Vrekoussis, Thomas; Heublein, Sabine; Bayer, Birgit; Anz, David; Knabl, Julia; Navrozoglou, Iordanis; Dian, Darius; Friese, Klaus; Makrigiannakis, Antonis; Jeschke, Udo

doi:10.3390/ijms13079069

Cited by 68 publications

(68 citation statements)

References 31 publications

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“…In former studies, we could show that these macrophages express FasL [20]. The expression of FasL on decidual macrophages had been already described before [29].…”

Section: Discussionmentioning

confidence: 88%

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PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

Kolben¹,

Rogatsch²,

Vattai³

et al. 2018

Preprint

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PPAR belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPAR is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPAR under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion & 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPAR. Expression changes were evaluated by immunohistochemistry and RT-PCR in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using CD68 as marker for macrophages. The intermediate villous trophoblast revealed a significantly lower PPAR expression in spontaneous and recurrent abortion. Maternal macrophages express PPAR. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPAR only in very few cases. PPAR is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPAR in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.

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“…In former studies, we could show that these macrophages express FasL [20]. The expression of FasL on decidual macrophages had been already described before [29].…”

Section: Discussionmentioning

confidence: 88%

“…An additional finding was the FasL-positivity of these macrophages [20]. Therefore the aim of this study was a phenotype characterization of macrophage populations in abortive placental tissue, its PPAR expression and the characterization of PPAR expressing trophoblast sub-types.…”

Section: Of 13mentioning

confidence: 99%

PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

Kolben¹,

Rogatsch²,

Vattai³

et al. 2018

Preprint

Self Cite

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“…CD95 itself does not initiate apoptosis. CD95L is the physiologic ligand of CD95 and expressed on the surface of cytotoxic T lymphocytes (CTLs) (Kilinc et al, 2009;Fritzsching et al, 2005) and macrophages (Zhang et al, 2005;Guenther et al, 2012). Upregulated CD95L proteins in H37Ra-infected macrophages cells may interact with each other to induce apoptosis (Xu et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Unphosphorylated STAT1 represses apoptosis in macrophages during Mycobacterium t uberculosis infection

Yao

Chen

et al. 2017

Journal of Cell Science

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In murine macrophages infected with Mycobacterium tuberculosis (Mtb), the level of phosphorylated STAT1 (P-STAT1), which drives the expression of many pro-apoptosis genes, increases quickly but then declines over a period of hours. By contrast, infection induces a continued increase in the level of unphosphorylated STAT1 that persists for several days. Here, we found that the level of unphosphorylated STAT1 correlated with the intracellular bacterial burden during the later stages of infection. To investigate the significance of a high level of unphosphorylated STAT1, we increased its concentration exogenously, and found that the apoptosis rate induced by Mtb was sufficiently decreased. Further experiments confirmed that unphosphorylated STAT1 affects the expression of several immune-associated genes and lessens the sensitivity of macrophages to CD95 (FAS)-mediated apoptosis during Mtb infection. Furthermore, we characterized 149 proteins that interacted with unphosphorylated STAT1 and the interactome network. The cooperation between unphosphorylated STAT1 and STAT3 results in downregulation of CD95 expression. Additionally, we verified that unphosphorylated STAT1 and IFIT1 competed for binding to eEF1A. Taken together, our data show that the role of unphosphorylated STAT1 differs from that of P-STAT1, and represses apoptosis in macrophages to promote immune evasion during Mtb infection.

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“…In one study, decidual macrophages from spontaneous abortions had increased Fas-L expression, which coincided with an increased rate of trophoblast apoptosis (12). It was proposed that the increased FasL-expressing population of macrophages reflected M1 activation (12); however, this is yet to be proven.…”

Section: M1/m2 Imbalances During Early Pregnancymentioning

confidence: 99%

M1/M2 Macrophage Polarity in Normal and Complicated Pregnancy

et al. 2014

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Tissue macrophages play an important role in all stages of pregnancy, including uterine stromal remodeling (decidualization) before embryo implantation, parturition, and post-partum uterine involution. The activation state and function of utero-placental macrophages are largely dependent on the local tissue microenvironment. Thus, macrophages are involved in a variety of activities such as regulation of immune cell activities, placental cell invasion, angiogenesis, and tissue remodeling. Disruption of the uterine microenvironment, particularly during the early stages of pregnancy (decidualization, implantation, and placentation) can have profound effects on macrophage activity and subsequently impact pregnancy outcome. In this review, we will provide an overview of the temporal and spatial regulation of utero-placental macrophage activation during normal pregnancy in human beings and rodents with a focus on more recent findings. We will also discuss the role of M1/M2 dysregulation within the intrauterine environment during adverse pregnancy outcomes.

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Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL: A Potential Role for Macrophages in Trophoblast Apoptosis

Cited by 68 publications

References 31 publications

PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

Unphosphorylated STAT1 represses apoptosis in macrophages during Mycobacterium t uberculosis infection

M1/M2 Macrophage Polarity in Normal and Complicated Pregnancy

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