bims-reprim 2022-04-24 papers

Issue of 2022–04–24
four papers selected by
Iva Filipovic, Karolinska Institutet

Am J Reprod Immunol. 2022 Apr 22.

Peritoneal natural killer cell chemotaxis is decreased in women with pelvic endometriosis.

Takashi Ushiwaka, Shinpei Yamamoto, Chika Yoshii, Shoko Hashimoto, Tamami Tsuzuki, Kayo Taniguchi, Chiaki Izumiya, Hiroaki Kobayashi, Nagamasa Maeda.

PROBLEM: NK cell and macrophage function are decreased in endometriosis, and the disease may involve reduced immune surveillance in the peritoneal cavity. NK cell cytotoxicity and migration ability (chemotaxis) are considered important; the former has been investigated, but the latter has not.
METHOD OF STUDY: We compared chemotaxis of immunocompetent cells (NK cells, macrophages, T cells) in peritoneal fluid obtained during laparoscopy in 27 women with and 13 without endometriosis. Peripheral blood NK cells were also obtained by the peripheral blood antibody beads method. Micro-cultured cells were examined by time-lapse photography, and the mean migration speed per cell was calculated as the chemotaxis. We investigated the relationship between chemotaxis and endometriosis.
RESULTS: NK cell chemotaxis was significantly lower in the endometriosis group. Macrophages and lymphocytes were not significantly different between the groups. During menstruation, NK cell chemotaxis decreased in both groups. Postmenstrual chemotaxis was increased significantly in women without endometriosis but remained low in women with endometriosis. The Revised-American Society for Reproductive Medicine score was not correlated with chemotaxis; in women with endometriosis, chemotaxis was decreased even at early stages. Peripheral blood NK cells showed no significant differences.
CONCLUSIONS: In women with endometriosis, not only cytotoxicity but also chemotaxis by NK cells in peritoneal cavity is significantly decreased, and particularly chemotaxis is decreased throughout the menstrual cycle. Therefore, antigens in retrograde menstrual blood that enters the peritoneal cavity might be left unprocessed. Repetition of this immune process in the peritoneal cavity may lead to the onset and subsequent progression of endometriosis. This article is protected by copyright. All rights reserved.

Keywords: chemotaxis; endometriosis; migration ability; natural killer cells; peritoneal cavity; retrograde menstruation

DOI: https://doi.org/10.1111/aji.13556

Immunol Rev. 2022 Apr 21.

Monocytes and macrophages in pregnancy: The good, the bad, and the ugly.

Heather True, Madison Blanton, Suhas Sureshchandra, Ilhem Messaoudi.

A successful human pregnancy requires precisely timed adaptations by the maternal immune system to support fetal growth while simultaneously protecting mother and fetus against microbial challenges. The first trimester of pregnancy is characterized by a robust increase in innate immune activity that promotes successful implantation of the blastocyst and placental development. Moreover, early pregnancy is also a state of increased vulnerability to vertically transmitted pathogens notably, human immunodeficiency virus (HIV), Zika virus (ZIKV), SARS-CoV-2, and Listeria monocytogenes. As gestation progresses, the second trimester is marked by the establishment of an immunosuppressive environment that promotes fetal tolerance and growth while preventing preterm birth, spontaneous abortion, and other gestational complications. Finally, the period leading up to labor and parturition is characterized by the reinstatement of an inflammatory milieu triggering childbirth. These dynamic waves of carefully orchestrated changes have been dubbed the "immune clock of pregnancy." Monocytes in maternal circulation and tissue-resident macrophages at the maternal-fetal interface play a critical role in this delicate balance. This review will summarize the current data describing the longitudinal changes in the phenotype and function of monocyte and macrophage populations in healthy and complicated pregnancies.

Keywords: bacterial; monocytes/macrophages; placenta; pregnancy; reproductive Immunology; viral

DOI: https://doi.org/10.1111/imr.13080

Hum Reprod Open. 2022 ;2022(2): hoac015

The microbiome in reproductive health: protocol for a systems biology approach using a prospective, observational study design.

Maria Christine Krog, Mette Elkjær Madsen, Sofie Bliddal, Zahra Bashir, Laura Emilie Vexø, Dorthe Hartwell, Luisa W Hugerth, Emma Fransson, Marica Hamsten, Fredrik Boulund, Kristin Wannerberger, Lars Engstrand, Ina Schuppe-Koistinen, Henriette Svarre Nielsen.

STUDY QUESTION: What is the microbiome profile across different body sites in relation to the normal menstrual cycle (with and without hormonal contraception), recurrent pregnancy loss (RPL) (before and during pregnancy, pregnancy loss or birth) and endometriosis (before, during and after surgery)? How do these profiles interact with genetics, environmental exposures, immunological and endocrine biomarkers?
WHAT IS KNOWN ALREADY: The microbiome is a key factor influencing human health and disease in areas as diverse as immune functioning, gastrointestinal disease and mental and metabolic disorders. There is mounting evidence to suggest that the reproductive microbiome may be influential in general and reproductive health, fertility and pregnancy outcomes.
STUDY DESIGN SIZE DURATION: This is a prospective, longitudinal, observational study using a systems biology approach in three cohorts totalling 920 participants. Since microbiome profiles by shot-gun sequencing have never been investigated in healthy controls during varying phases of the menstrual cycle, patients with RPL and patients with endometriosis, no formal sample size calculation can be performed. The study period is from 2017 to 2024 and allows for longitudinal profiling of study participants to enable deeper understanding of the role of the microbiome and of host-microbe interactions in reproductive health.
PARTICIPANTS/MATERIALS SETTING METHODS: Participants in each cohort are as follows: Part 1 MiMens-150 healthy women with or without hormonal contraception; Part 2 MiRPL-200 couples with RPL, 50 healthy couples with prior uncomplicated pregnancy and 150 newborns; Part 3 MiEndo-120 patients with endometriosis requiring surgery with or without hormonal treatment. Microbiome profiles from saliva, faeces, rectal mucosa, vaginal fluid and endometrium will be studied, as well as the Omics profile, endocrine disrupting chemicals and endocrine and immune factors in blood, hair, saliva and urine. Pregnancy loss products, seminal microbiome, HLA types, endometriotic tissue and genetic risk and comprehensive questionnaire data will also be studied, where appropriate. Correlations with mental and physical health will be evaluated.
STUDY FUNDING/COMPETING INTERESTS: This work is supported by funding from Ferring Pharmaceuticals ([#MiHSN01] to H.S.N., M.C.K., M.E.M., L.E.V., L.E., I.S.-K., F.B., L.W.H., E.F. and M.H.), Rigshospitalet's Research Funds ([#E-22614-01 and #E-22614-02] to M.C.K. and [#E-22222-06] to S.B.), Niels and Desiree Yde's Foundation (S.B., endocrine analyses [#2015-2784]), the Musikforlæggerne Agnes and Knut Mørk's Foundation (S.B., endocrine and immune analyses [#35108-001]) and Oda and Hans Svenningsen's Foundation ([#F-22614-08] to H.S.N.). Medical writing assistance with this manuscript was provided by Caroline Loat, PhD, and funded by Ferring Pharmaceuticals. H.S.N. reports personal fees from Ferring Pharmaceuticals, Merck Denmark A/S, Ibsa Nordic, Astra Zeneca and Cook Medical outside the submitted work. K.W. is a full-time employee of Ferring Pharmaceuticals. No other conflicts are reported.
TRIAL REGISTRATION NUMBER: N/A.
TRIAL REGISTRATION DATE: N/A.
DATE OF FIRST PATIENT’S ENROLMENT: N/A.

Keywords: contraception; endocrinology; endometriosis; fertility; immunology; menstrual cycle; microbiome; pregnancy loss; recurrent pregnancy loss

DOI: https://doi.org/10.1093/hropen/hoac015

Inflamm Res. 2022 Apr 21.

Pregnancy tailors endotoxin-induced monocyte and neutrophil responses in the maternal circulation.

Marcelo Farias-Jofre, Roberto Romero, Jose Galaz, Yi Xu, Li Tao, Catherine Demery-Poulos, Marcia Arenas-Hernandez, Gaurav Bhatti, Zhenjie Liu, Naoki Kawahara, Tomi Kanninen, Zachary Shaffer, Tinnakorn Chaiworapongsa, Kevin R Theis, Adi L Tarca, Nardhy Gomez-Lopez.

OBJECTIVE: To comprehensively characterize monocyte and neutrophil responses to E. coli and its product [lipopolysaccharide (LPS) or endotoxin] in vitro during pregnancy.
MATERIAL OR SUBJECTS: Peripheral blood was collected from pregnant women during the third trimester (n = 20) and from non-pregnant women (n = 20).
METHODS: The number, phagocytic activity, and reactive oxygen species (ROS) production of peripheral monocytes and neutrophils were investigated using flow cytometry. The phenotypes of peripheral monocytes and neutrophils after acute or chronic LPS stimulation were also determined using flow cytometry. Cytokine profiles were quantified for LPS-stimulated peripheral blood mononuclear cells (PBMCs) and a whole blood TruCulture® system using a multiplex immunoassay.
RESULTS: Increased number, phagocytic activity, and ROS production capacity of monocytes and neutrophils were found in pregnant compared to non-pregnant women. Additionally, specific subsets of pro-inflammatory monocytes (IL-6+CD14+ or MIP-1α+CD14+ cells) and neutrophils (IL-1β+CD15+ or MIP-1β+CD15+ cells) were increased in pregnant women in response to acute LPS stimulation. Moreover, distinct subsets of intermediate-activated monocytes expressing CD142, IL-6, and IL-1RA were increased in pregnant women upon chronic LPS stimulation. Last, pregnant women displayed a different cytokine profile than non-pregnant women in LPS-stimulated PBMCs and in whole blood.
CONCLUSIONS: Pregnancy tailors the immune responses of circulating monocytes and neutrophils to endotoxin, a Gram-negative bacterial product.

Keywords: Chorioamnionitis; Cytokine; Funisitis; Infection; Inflammation; Phagocytosis

DOI: https://doi.org/10.1007/s00011-022-01569-z