Cutting Edge: Fetal/Placental Type I IFN Can Affect Maternal Survival and Fetal Viral Load during Viral Infection

Racicot, Karen; Aldo, Paulomi; El-Guindy, Ayman; Kwon, Ja Young; Romero, Roberto; Mor, Gil

doi:10.4049/jimmunol.1601824

Cited by 42 publications

(45 citation statements)

References 40 publications

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“…69,70 In addition to its antiviral role, IFN-has been reported to function as an immune modulator by limiting immune responses 71 and regulating the recruitment of immune cells. 30,72 The immune regulatory functions of IFN-are meditated by the expression of ISGs, which can promote apoptosis, 73 inhibit cell recruitment, 74 and induce cell differentiation. 75 PD-L1 belongs to the ISG family and is an important immune modulatory factor.…”

Section: Discussionmentioning

confidence: 99%

Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function

Zhang

Aldo

You

et al. 2020

Journal of Leukocyte Biology

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Decidual macrophages are in close contact with trophoblast cells during placenta development, and an appropriate crosstalk between these cellular compartments is crucial for the establishment and maintenance of a healthy pregnancy. During different phases of gestation, macrophages undergo dynamic changes to adjust to the different stages of fetal development. Trophoblast‐secreted factors are considered the main modulators responsible for macrophage differentiation and function. However, the phenotype of these macrophages induced by trophoblast‐secreted factors and the factors responsible for their polarization has not been elucidated. In this study, we characterized the phenotype and function of human trophoblast‐induced macrophages. Using in vitro models, we found that human trophoblast‐educated macrophages were CD14+CD206+CD86− and presented an unusual transcriptional profile in response to TLR4/LPS activation characterized by the expression of type I IFN‐β expression. IFN‐β further enhances the constitutive production of soluble programmed cell death ligand 1 (PD‐L1) from trophoblast cells. PD‐1 blockage inhibited trophoblast‐induced macrophage differentiation. Soluble PD‐L1 (sPD‐L1) was detected in the blood of pregnant women and increased throughout the gestation. Collectively, our data suggest the existence of a regulatory circuit at the maternal fetal interface wherein IFN‐β promotes sPD‐L1 expression/secretion by trophoblast cells, which can then initiate a PD‐L1/PD‐1‐mediated macrophage polarization toward an M2 phenotype, consequently decreasing inflammation. Macrophages then maintain the expression of sPD‐L1 by the trophoblasts through IFN‐β production induced through TLR4 ligation.

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Section: Discussionmentioning

confidence: 99%

Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function

Zhang

Aldo

You

et al. 2020

Journal of Leukocyte Biology

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“…Furthermore, evacuation of the uterus significantly improves the mother's chances of survival (110). Since the placenta regulates the maternal immune system and can itself respond to pathogens, it is probably an important mediator of the maternal response to viral infection, regardless of whether the placenta is directly infected (112).…”

Section: Viral Infection and Ptb: In Utero Or Systemic Infectionmentioning

confidence: 99%

Risks associated with viral infections during pregnancy

Racicot¹,

Mor

2017

Journal of Clinical Investigation

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238

204

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“…Viral infections, such as influenza virus, can prime or accentuate bacterial infection-mediated preterm labor and the intensity of inflammatory response at the maternal-fetal interface (61)(62)(63)(64)(65)(66). Specifically, pathogen/pathogen-associated molecular patterndriven activation of type I Interferon (IFN)/IFN receptor (IFNAR) was sufficient to prime for systemic and uterine proinflammatory chemokine and cytokine production and induction of preterm birth in mice (67).…”

Section: Priming Infectionsmentioning

confidence: 99%

Immunobiology of Acute Chorioamnionitis

2020

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Acute chorioamnionitis is characterized by neutrophilic infiltration and inflammation at the maternal fetal interface. It is a relatively common complication of pregnancy and can have devastating consequences including preterm labor, maternal infections, fetal infection/inflammation, fetal lung, brain, and gastrointestinal tract injury. In this review, we will discuss current understanding of the pathogenesis, immunobiology, and mechanisms of this condition. Most commonly, acute chorioamnionitis is a result of ascending infection with relatively low-virulence organisms such as the Ureaplasma species. Furthermore, recent vaginal microbiome studies suggest that there is a link between vaginal dysbiosis, vaginal inflammation, and ascending infection. Although less common, microorganisms invading the maternal-fetal interface via hematogenous route (e.g., Zika virus, Cytomegalovirus, and Listeria) can cause placental villitis and severe fetal inflammation and injury. We will provide an overview of the knowledge gleaned from different animal models of acute chorioamnionitis and the role of different immune cells in different maternal-fetal compartments. Lastly, we will discuss how infectious agents can break the maternal tolerance of fetal allograft during pregnancy and highlight the novel future therapeutic approaches.

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Cutting Edge: Fetal/Placental Type I IFN Can Affect Maternal Survival and Fetal Viral Load during Viral Infection

Cited by 42 publications

References 40 publications

Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function

Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function

Risks associated with viral infections during pregnancy

Immunobiology of Acute Chorioamnionitis

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