bims-reprim 2022-02-27 papers

Issue of 2022–02–27
four papers selected by
Iva Filipovic, Karolinska Institutet

Front Immunol. 2022 ;13 821542

Human-Induced CD49a+ NK Cells Promote Fetal Growth.

Xianghui Du, Huaiping Zhu, Defeng Jiao, Zhigang Nian, Jinghe Zhang, Yonggang Zhou, Xiaohu Zheng, Xianhong Tong, Haiming Wei, Binqing Fu.

CD49a+ natural killer (NK) cells play a critical role in promoting fetal development and maintaining immune tolerance at the maternal-fetal interface during the early stages of pregnancy. However, given their residency in human tissue, thorough studies and clinical applications are difficult to perform. It is still unclear as to how functional human CD49a+ NK cells can be induced to benefit pregnancy outcomes. In this study, we established three no-feeder cell induction systems to induce human CD49a+ NK cells from umbilical cord blood hematopoietic stem cells (HSCs), bone marrow HSCs, and peripheral blood NK cells in vitro. These induced NK cells (iNKs) from three cell induction systems display high levels of CD49a, CD9, CD39, CD151 expression, low levels of CD16 expression, and no obvious cytotoxic capability. They are phenotypically and functionally similar to decidual NK cells. Furthermore, these iNKs display a high expression of growth-promoting factors and proangiogenic factors and can promote fetal growth and improve uterine artery blood flow in a murine pregnancy model in vivo. This research demonstrates the ability of human-induced CD49a+ NK cells to promote fetal growth via three cell induction systems, which could eventually be used to treat patients experiencing adverse pregnancy outcomes.

Keywords: CD49a; decidual tissue-resident NK cells; fetal growth; low cytotoxic; maternal-fetal interface

DOI: https://doi.org/10.3389/fimmu.2022.821542

Front Immunol. 2022 ;13 828681

Editorial: Viral Infection at the Maternal-Fetal Interface.

Abhay P S Rathore, Vivian Vasconcelos Costa, Ashley L St John.

Keywords: CMV; COVID - 19; HIV; Zika; maternal immunity; maternal-fetal; viruses

DOI: https://doi.org/10.3389/fimmu.2022.828681

Immunol Rev. 2022 Feb 23.

Extracellular vesicles and immune response during pregnancy: A balancing act.

Adrian E Morelli, Yoel Sadovsky.

The mechanisms underlying maternal tolerance of the semi- or fully-allogeneic fetus are intensely investigated. Across gestation, feto-placental antigens interact with the maternal immune system locally within the trophoblast-decidual interface and distantly through shed cells and soluble molecules that interact with maternal secondary lymphoid tissues. The discovery of extracellular vesicles (EVs) as local or systemic carriers of antigens and immune-regulatory molecules has added a new dimension to our understanding of immune modulation prior to implantation, during trophoblast invasion, and throughout the course of pregnancy. New data on immune-regulatory molecules, located on EVs or within their cargo, suggest a role for EVs in negotiating immune tolerance during gestation. Lessons from the field of transplant immunology also shed light on possible interactions between feto-placentally derived EVs and maternal lymphoid tissues. These insights illuminate a potential role for EVs in major obstetrical disorders. This review provides updated information on intensely studied, pregnancy-related EVs, their cargo molecules, and patterns of fetal-placental-maternal trafficking, highlighting potential immune pathways that might underlie immune suppression or activation in gestational health and disease. Our summary also underscores the likely need to broaden the definition of the maternal-fetal interface to systemic maternal immune tissues that might interact with circulating EVs.

Keywords: extracellular vesicles; gestational immunology; pregnancy; tolerance

DOI: https://doi.org/10.1111/imr.13074

Nat Commun. 2022 02 21. 13(1): 975

Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response.

Denise Chan, Phillip R Bennett, Yun S Lee, Samit Kundu, T G Teoh, Malko Adan, Saqa Ahmed, Richard G Brown, Anna L David, Holly V Lewis, Belen Gimeno-Molina, Jane E Norman, Sarah J Stock, Vasso Terzidou, Pascale Kropf, Marina Botto, David A MacIntyre, Lynne Sykes.

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.

DOI: https://doi.org/10.1038/s41467-022-28620-1