bims-reprim 2022-03-20 papers

Issue of 2022–03–20
four papers selected by
Iva Filipovic, Karolinska Institutet

Immunol Rev. 2022 Mar 14.

Fetal inflammatory response at the fetomaternal interface: A requirement for labor at term and preterm.

Human parturition at term and preterm is an inflammatory process synchronously executed by both fetomaternal tissues to transition them from a quiescent state t an active state of labor to ensure delivery. The initiators of the inflammatory signaling mechanism can be both maternal and fetal. The placental (fetal)-maternal immune and endocrine mediated homeostatic imbalances and inflammation are well reported. However, the fetal inflammatory response (FIR) theories initiated by the fetal membranes (amniochorion) at the choriodecidual interface are not well established. Although immune cell migration, activation, and production of proparturition cytokines to the fetal membranes are reported, cellular level events that can generate a unique set of inflammation are not well discussed. This review discusses derangements to fetal membrane cells (physiologically and pathologically at term and preterm, respectively) in response to both endogenous and exogenous factors to generate inflammatory signals. In addition, the mechanisms of inflammatory signal propagation (fetal signaling of parturition) and how these signals cause immune imbalances at the choriodecidual interface are discussed. In addition to maternal inflammation, this review projects FIR as an additional mediator of inflammatory overload required to promote parturition.

Keywords: EMT; aging; amniochorion; choriodecidua; exosomes; inflammation; premature rupture of the membranes; preterm birth; senescence; signaling

DOI: https://doi.org/10.1111/imr.13075

Nat Rev Immunol. 2022 Mar 18.

SARS-CoV-2 infection and COVID-19 vaccination in pregnancy.

Victoria Male.

SARS-CoV-2 infection poses increased risks of poor outcomes during pregnancy, including preterm birth and stillbirth. There is also developing concern over the effects of SARS-CoV-2 infection on the placenta, and these effects seem to vary between different viral variants. Despite these risks, many pregnant individuals have been reluctant to be vaccinated against the virus owing to safety concerns. We now have extensive data confirming the safety and effectiveness of COVID-19 vaccination during pregnancy, although it will also be necessary to determine the effectiveness of these vaccines specifically against newly emerging viral variants, including Omicron. In this Progress article, I cover recent developments in our understanding of the risks of SARS-CoV-2 infection in pregnancy, and how vaccination can reduce these.

DOI: https://doi.org/10.1038/s41577-022-00703-6

J Immunol. 2022 Mar 18. pii: ji2100439. [Epub ahead of print]

IL-22 Plays a Dual Role in the Amniotic Cavity: Tissue Injury and Host Defense against Microbes in Preterm Labor.

Meyer Gershater, Roberto Romero, Marcia Arenas-Hernandez, Jose Galaz, Kenichiro Motomura, Li Tao, Yi Xu, Derek Miller, Roger Pique-Regi, Gregorio Martinez, Yesong Liu, Eunjung Jung, Robert Para, Nardhy Gomez-Lopez.

IL-22 is a multifaceted cytokine with both pro- and anti-inflammatory functions that is implicated in multiple pathologies. However, the role of IL-22 in maternal-fetal immunity in late gestation is poorly understood. In this study, we first showed that IL-22+ T cells coexpressing retinoic acid-related orphan receptor γt (ROR-γt) are enriched at the human maternal-fetal interface of women with preterm labor and birth, which was confirmed by in silico analysis of single-cell RNA sequencing data. T cell activation leading to preterm birth in mice was preceded by a surge in IL-22 in the maternal circulation and amniotic cavity; however, systemic administration of IL-22 in mice did not induce adverse perinatal outcomes. Next, using an ex vivo human system, we showed that IL-22 can cross from the choriodecidua to the intra-amniotic space, where its receptors (Il22ra1, Il10rb, and Il22ra2) are highly expressed by murine gestational and fetal tissues in late pregnancy. Importantly, amniotic fluid concentrations of IL-22 were elevated in women with sterile or microbial intra-amniotic inflammation, suggesting a dual role for this cytokine. The intra-amniotic administration of IL-22 alone shortened gestation and caused neonatal death in mice, with the latter outcome involving lung maturation and inflammation. IL-22 plays a role in host response by participating in the intra-amniotic inflammatory milieu preceding Ureaplasma parvum-induced preterm birth in mice, which was rescued by the deficiency of IL-22. Collectively, these data show that IL-22 alone is capable of causing fetal injury leading to neonatal death and can participate in host defense against microbial invasion of the amniotic cavity leading to preterm labor and birth.

DOI: https://doi.org/10.4049/jimmunol.2100439

Front Immunol. 2022 ;13 820366

Does the Amniotic Fluid of Mice Contain a Viable Microbiota?

Andrew D Winters, Roberto Romero, Jonathan M Greenberg, Jose Galaz, Zachary D Shaffer, Valeria Garcia-Flores, David J Kracht, Nardhy Gomez-Lopez, Kevin R Theis.

The existence of an amniotic fluid microbiota (i.e., a viable microbial community) in mammals is controversial. Its existence would require a fundamental reconsideration of fetal in utero exposure to and colonization by microorganisms and the role of intra-amniotic microorganisms in fetal immune development as well as in pregnancy outcomes. In this study, we determined whether the amniotic fluid of mice harbors a microbiota in late gestation. The profiles of the amniotic fluids of pups located proximally or distally to the cervix were characterized through quantitative real-time PCR, 16S rRNA gene sequencing, and culture (N = 21 dams). These profiles were compared to those of technical controls for bacterial and DNA contamination. The load of 16S rRNA genes in the amniotic fluid exceeded that in controls. Additionally, the 16S rRNA gene profiles of the amniotic fluid differed from those of controls, with Corynebacterium tuberculostearicum being differentially more abundant in amniotic fluid profiles; however, this bacterium was not cultured from amniotic fluid. Of the 42 attempted bacterial cultures of amniotic fluids, only one yielded bacterial growth - Lactobacillus murinus. The 16S rRNA gene of this common murine-associated bacterium was not detected in any amniotic fluid sample, suggesting it did not originate from the amniotic fluid. No differences in the 16S rRNA gene load, 16S rRNA gene profile, or bacterial culture were observed between the amniotic fluids located Proximally and distally to the cervix. Collectively, these data indicate that, although there is a modest DNA signal of bacteria in murine amniotic fluid, there is no evidence that this signal represents a viable microbiota. While this means that amniotic fluid is not a source of microorganisms for in utero colonization in mice, it may nevertheless contribute to fetal exposure to microbial components. The developmental consequences of this observation warrant further investigation.

Keywords: amniotic fluid; in utero colonization; low microbial biomass study; microbiome; microbiota; mouse model; sterile womb hypothesis

DOI: https://doi.org/10.3389/fimmu.2022.820366