bims-reprim 2021-08-29 papers

Issue of 2021‒08‒29
five papers selected by
Iva Filipovic
Karolinska Institutet

Science. 2021 Aug 27. pii: eabf3002. [Epub ahead of print]373(6558):

Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring.

Ai Ing Lim, Taryn McFadden, Verena M Link, Seong-Ji Han, Rose-Marie Karlsson, Apollo Stacy, Taylor K Farley, Djalma S Lima-Junior, Oliver J Harrison, Jigar V Desai, Michail S Lionakis, Han-Yu Shih, Heather A Cameron, Yasmine Belkaid.

The immune system has evolved in the face of microbial exposure. How maternal infection experienced at distinct developmental stages shapes the offspring immune system remains poorly understood. Here, we show that during pregnancy, maternally restricted infection can have permanent and tissue-specific impacts on offspring immunity. Mechanistically, maternal interleukin-6 produced in response to infection can directly impose epigenetic changes on fetal intestinal epithelial stem cells, leading to long-lasting impacts on intestinal immune homeostasis. As a result, offspring of previously infected dams develop enhanced protective immunity to gut infection and increased inflammation in the context of colitis. Thus, maternal infection can be coopted by the fetus to promote long-term, tissue-specific fitness, a phenomenon that may come at the cost of predisposition to inflammatory disorders.

DOI: https://doi.org/10.1126/science.abf3002

Nat Rev Microbiol. 2021 Aug 25.

Infections at the maternal-fetal interface: an overview of pathogenesis and defence.

Christina J Megli, Carolyn B Coyne.

Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym 'TORCH' (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission.

DOI: https://doi.org/10.1038/s41579-021-00610-y

J Clin Med. 2021 Aug 14. pii: 3579. [Epub ahead of print]10(16):

Evaluating Markers of Immune Tolerance and Angiogenesis in Maternal Blood for an Association with Risk of Pregnancy Loss.

Michelle A Wyatt, Sarah C Baumgarten, Amy L Weaver, Chelsie C Van Oort, Bohdana Fedyshyn, Rodrigo Ruano, Chandra C Shenoy, Elizabeth Ann L Enninga.

Pregnancy loss affects approximately 20% of couples. The lack of a clear cause complicates half of all miscarriages. Early evidence indicates the maternal immune system and angiogenesis regulation are both key players in implantation success or failure. Therefore, this prospective study recruited women in the first trimester with known viable intrauterine pregnancy and measured blood levels of immune tolerance proteins galectin-9 (Gal-9) and interleukin (IL)-4, and angiogenesis proteins (vascular endothelial growth factors (VEGF) A, C, and D) between 5 and 9 weeks gestation. Plasma concentrations were compared between groups defined based on (a) pregnancy outcome and (b) maternal history of miscarriage, respectively. In total, 56 women were recruited with 10 experiencing a miscarriage or pregnancy loss in the 2nd or 3rd trimester and 11 having a maternal history or miscarriage. VEGF-C was significantly lower among women with a miscarriage or pregnancy loss. Gal-9 and VEGF-A concentrations were decreased in women with a prior miscarriage. Identification of early changes in maternal immune and angiogenic factors during pregnancy may be a tool to improve patient counseling on pregnancy loss risk and future interventions to reduce miscarriage in a subset of women.

Keywords: galectin-9; immunology; interleukin-4; miscarriage; pregnancy loss; vascular endothelial growth factor

DOI: https://doi.org/10.3390/jcm10163579

Infect Immun. 2021 Aug 23. IAI0080020

The reaction of innate lymphoid cells in the mouse female genital tract to chlamydial infection.

Svenja Barth, Susanne Kirschnek, Noemi Ortmann, Yakup Tanriver, Georg Häcker.

Background Innate lymphoid cells (ILCs) are comprised of five distinct subsets. ILCs are found at mucosal barriers and may fight invading pathogens. Chlamydia is an intracellular bacterium that infects the mucosa of the genital tract and can cause severe tissue damage. Methods We used a mouse infection model with Chlamydia muridarum (Cmu) to measure the reaction of genital tract ILCs to the infection. Results Tissue resident natural killer cells were the largest group in the uninfected female genital tract, and their number did not substantially change. Conventional NK cells were present at the greatest numbers during acute infection, while ILC1 cells continuously increased to high numbers. ILC2 and ILC3 cells were found at lower numbers that oscillated by a factor of 2-4. The majority of ILC3 transdifferentiated into ILC1 cells. NK cells and ILC1 cells produced IFN-γ and, rarely, TNF, but only early in the infection. Lack of B and T cells increased, while the loss of myeloid cells decreased ILC numbers. ILCs accumulated to high density in the oviduct, a main site of tissue destruction. Conclusions ILC subsets are part of the inflammatory and immune reaction during infection with Cmu and may contribute to tissue damage during chlamydial infection.

DOI: https://doi.org/10.1128/IAI.00800-20

Cell Mol Immunol. 2021 Aug 23.

Biology and pathology of the uterine microenvironment and its natural killer cells.

Fuyan Wang, Anita Ellen Qualls, Laia Marques-Fernandez, Francesco Colucci.

Tissues are the new frontier of discoveries in immunology. Cells of the immune system are an integral part of tissue physiology and immunity. Determining how immune cells inhabit, housekeep, and defend gut, lung, brain, liver, uterus, and other organs helps revealing the intimate details of tissue physiology and may offer new therapeutic targets to treat pathologies. The uterine microenvironment modulates the development and function of innate lymphoid cells [ILC, largely represented by natural killer (NK) cells], macrophages, T cells, and dendritic cells. These immune cells, in turn, contribute to tissue homeostasis. Regulated by ovarian hormones, the human uterine mucosa (endometrium) undergoes ~400 monthly cycles of breakdown and regeneration from menarche to menopause, with its fibroblasts, glands, blood vessels, and immune cells remodeling the tissue into the transient decidua. Even more transformative changes occur upon blastocyst implantation. Before the placenta is formed, the endometrial glands feed the embryo by histiotrophic nutrition while the uterine spiral arteries are stripped of their endothelial layer and smooth muscle actin. This arterial remodeling is carried out by invading fetal trophoblast and maternal immune cells, chiefly uterine NK (uNK) cells, which also assist fetal growth. The transformed arteries no longer respond to maternal stimuli and meet the increasing demands of the growing fetus. This review focuses on how the everchanging uterine microenvironment affects uNK cells and how uNK cells regulate homeostasis of the decidua, placenta development, and fetal growth. Determining these pathways will help understand the causes of major pregnancy complications.

Keywords: Decidua; Natural killer cells; Pregnancy; Uterine microenvironment; uNK

DOI: https://doi.org/10.1038/s41423-021-00739-z