bims-reprim 2021-11-21 papers

Issue of 2021–11–21
four papers selected by
Iva Filipovic, Karolinska Institutet

Proc Natl Acad Sci U S A. 2021 Nov 23. pii: e2115410118. [Epub ahead of print]118(47):

Decidual NK cells kill Zika virus-infected trophoblasts.

Sumit Sen Santara, Ângela C Crespo, Sachin Mulik, Cristian Ovies, Selma Boulenouar, Jack L Strominger, Judy Lieberman.

Zika virus (ZIKV) during pregnancy infects fetal trophoblasts and causes placental damage and birth defects including microcephaly. Little is known about the anti-ZIKV cellular immune response at the maternal-fetal interface. Decidual natural killer cells (dNK), which directly contact fetal trophoblasts, are the dominant maternal immune cells in the first-trimester placenta, when ZIKV infection is most hazardous. Although dNK express all the cytolytic molecules needed to kill, they usually do not kill infected fetal cells but promote placentation. Here, we show that dNK degranulate and kill ZIKV-infected placental trophoblasts. ZIKV infection of trophoblasts causes endoplasmic reticulum (ER) stress, which makes them dNK targets by down-regulating HLA-C/G, natural killer (NK) inhibitory receptor ligands that help maintain tolerance of the semiallogeneic fetus. ER stress also activates the NK activating receptor NKp46. ZIKV infection of Ifnar1 -/- pregnant mice results in high viral titers and severe intrauterine growth restriction, which are exacerbated by depletion of NK or CD8 T cells, indicating that killer lymphocytes, on balance, protect the fetus from ZIKV by eliminating infected cells and reducing the spread of infection.

Keywords: ER stress; ZIKV; decidual NK; extravillous trophoblast; pregnancy

DOI: https://doi.org/10.1073/pnas.2115410118

Front Immunol. 2021 ;12 735564

Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients.

Dorien Feyaerts, Joshua Gillard, Bram van Cranenbroek, Lina Rigodanzo Marins, Mariam M S Baghdady, Gaia Comitini, A Titia Lely, Henk W van Hamersvelt, Olivier W H van der Heijden, Irma Joosten, Renate G van der Molen.

Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR+ Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring's health.

Keywords: decidua; kidney transplantation; neonatal immunity; pregnancy; renal transplantation; uterine immunity

DOI: https://doi.org/10.3389/fimmu.2021.735564

Front Immunol. 2021 ;12 777927

Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses.

Jeremy Anderson, Cao Minh Thang, Le Quang Thanh, Vo Thi Trang Dai, Van Thanh Phan, Bui Thi Hong Nhu, Do Ngoc Xuan Trang, Phan Thi Phuong Trinh, Thuong Vu Nguyen, Nguyen Trong Toan, Christopher M Harpur, Kim Mulholland, Daniel G Pellicci, Lien Anh Ha Do, Paul V Licciardi.

Background: Preterm infants are highly vulnerable to infectious disease. While many factors are likely to contribute to this enhanced susceptibility, the immature nature of the preterm immune system is postulated as one key factor.
Methods: In our study, we used high-dimensional flow cytometry and cytokine assays to characterise the immune profiles in 25 preterm (range: 30.4-34.1 weeks gestational age) and 25 term infant (range: 37-40 weeks gestational age) cord blood samples.
Results: We found that preterm infants exhibit reduced frequencies of monocytes, CD56bright NK cells, CD8+ T-cells, γδ T-cells and an increased frequency of intermediate monocytes, CD4+ T-cells, central memory CD4+ and CD8+ T-cells, Tregs and transitional B-cells compared to term infants. Pro-inflammatory cytokines IL-1β, IL-6 and IL-17A were lower in preterm infants in addition to chemokines IL-8, eotaxin, MIP-1α and MIP-1β. However, IL-15 and MCP-1 were higher in preterm infants.
Conclusion: Overall, we identify key differences in pro-inflammatory immune profiles between preterm and term infants. These findings may help to explain why preterm infants are more susceptible to infectious disease during early life and facilitate the development of targeted interventions to protect this highly vulnerable group.

Keywords: immune profile; infant; infection; inflammation; preterm

DOI: https://doi.org/10.3389/fimmu.2021.777927

Front Med (Lausanne). 2021 ;8 674997

Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy.

Background: Obstructive sleep apnea (OSA) is prevalent in pregnancy and it is associated with adverse pregnancy-related outcomes such as gestational diabetes, pre-eclampsia, and low birth weight. Maternal systemic inflammation is proposed to be one of the main intermediate mechanisms. However, the effects of OSA on systemic inflammation are unknown in normal pregnancy. Methods: Women in the 3rd trimester underwent hospital polysomnography to evaluate whether OSA increases systemic inflammation in normal pregnancy and its potential association with adverse fetal outcomes. OSA was defined as an apnea-hypopnea index (AHI) of ≥ 5 h-1. Plasma cytokines levels (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were determined by multiple immunoassays. Results: We included 11 patients with OSA and 22 women with AHI < 5 h-1, who were homogeneous in age, and body mass index (BMI). Women with OSA had significant higher levels of TNF-α, IL-1β, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α (r = 0.40), IL-1β (r = 0.36), IL-6 (r = 0.52), IL-8 (r = 0.43), between obstructive apnea index and TNF-α (r = 0.46) and between AHI and IL-1β (r = 0.43). We also found that CT90% was related to IL-8 (r = 0.37). There were no significant differences in neonatal characteristics; however, we found inverse correlations between TNF-α and IL-8 with birth weight (both r = -0.48), while IL-8 showed a significant inverse relationship with neonatal gestational age (r = -0.48). Conclusions: OSA in our normal pregnancy population was associated with higher systemic inflammation, which was related to obstructive events, especially during REM sleep. Moreover, systemic inflammation was inversely correlated with neonatal birth weight and age.

Keywords: Obstructive sleep apnea; REM; apneas-hypopneas index; cytokine; fetal outcomes; hypoxia; inflammation

DOI: https://doi.org/10.3389/fmed.2021.674997