bims-reprim 2021-07-11 papers

Issue of 2021–07–11
three papers selected by
Iva Filipovic, Karolinska Institutet

Front Immunol. 2021 ;12 607669

How Do Uterine Natural Killer and Innate Lymphoid Cells Contribute to Successful Pregnancy?

Oisín Huhn, Xiaohui Zhao, Laura Esposito, Ashley Moffett, Francesco Colucci, Andrew M Sharkey.

Innate lymphoid cells (ILCs) are the most abundant immune cells in the uterine mucosa both before and during pregnancy. Circumstantial evidence suggests they play important roles in regulating placental development but exactly how they contribute to the successful outcome of pregnancy is still unclear. Uterine ILCs (uILCs) include subsets of tissue-resident natural killer (NK) cells and ILCs, and until recently the phenotype and functions of uILCs were poorly defined. Determining the specific roles of each subset is intrinsically challenging because of the rapidly changing nature of the tissue both during the menstrual cycle and pregnancy. Single-cell RNA sequencing (scRNAseq) and high dimensional flow and mass cytometry approaches have recently been used to analyse uILC populations in the uterus in both humans and mice. This detailed characterisation has significantly changed our understanding of the heterogeneity within the uILC compartment. It will also enable key clinical questions to be addressed including whether specific uILC subsets are altered in infertility, miscarriage and pregnancy disorders such as foetal growth restriction and pre-eclampsia. Here, we summarise recent advances in our understanding of the phenotypic and functional diversity of uILCs in non-pregnant endometrium and first trimester decidua, and review how these cells may contribute to successful placental development.

Keywords: decidua; endometrium; innate lymphoid cell; placenta; pregnancy; tissue resident natural killer cell; uterine natural killer cell

DOI: https://doi.org/10.3389/fimmu.2021.607669

Front Immunol. 2021 ;12 703009

Editorial: Immunological Role of the Maternal Microbiome in Pregnancy.

Nicoletta DiSimone, Eytan Robert Barnea, Martin Mueller.

Keywords: immunity; implantation; microbiota; pregnancy; preterm (birth); preterm/full term infants

DOI: https://doi.org/10.3389/fimmu.2021.703009

EBioMedicine. 2021 Jul 02. pii: S2352-3964(21)00265-6. [Epub ahead of print]69 103472

Proinflammatory oscillations over the menstrual cycle drives bystander CD4 T cell recruitment and SHIV susceptibility from vaginal challenge.

Alison Swaims-Kohlmeier, Anandi N Sheth, Jed Brody, Felicia P Hardnett, Sunita Sharma, Erin Wells Bonning, Igho Ofotokun, Ivana Massud, J Gerardo García-Lerma.

BACKGROUND: The menstrual cycle influences HIV infection-risk in women, although the timing and underlying mechanism are unclear. Here we investigated the contribution of the menstrual cycle to HIV susceptibility through evaluating immune behavior with infection-risk over time.
METHODS: Blood and vaginal lavage samples were collected from 18 pig-tailed macaques to evaluate immune changes over reproductive cycles, and from 5 additional animals undergoing repeated vaginal exposures to simian HIV (SHIV). Peripheral blood mononuclear cell (PBMC) samples from healthy women (n = 10) were prospectively collected over the course of a menstrual cycle to profile T cell populations. Immune properties from PBMC and vaginal lavage samples were measured by flow cytometry. Plasma progesterone was measured by enzyme immunoassay. The oscillation frequency of progesterone concentration and CCR5 expression on CD4 T cells was calculated using the Lomb-Scargle periodogram. SHIV infection was monitored in plasma by RT-PCR. Immune measures were compared using generalized estimating equations (GEE).
FINDINGS: Macaques cycle-phases were associated with fluctuations in systemic immune properties and a type-1 inflammatory T cell response with corresponding CCR5+ memory CD4 T cell (HIV target cell) infiltration into the vaginal lumen at the late luteal phase. Power spectral analysis identified CCR5 oscillation frequencies synchronized with reproductive cycles. In a repetitive low-dose vaginal challenge model, productive SHIV163P3 infection only occurred during intervals of mounting type-1 T cell responses (n = 5/5). Finally, we identify similar type-1 inflammatory T cell responses over the menstrual cycle are occurring in healthy women.
INTERPRETATION: These data demonstrate that periodic shifts in the immune landscape under menstrual cycle regulation drives bystander CCR5+ CD4 T cell recruitment and HIV susceptibility in the female reproductive tract.
FUNDING: This study was supported by the U.S. Centers for Disease Control and Prevention, Atlanta, GA 30329 and NIH grants to Emory University (K23AI114407 to A.N.S., the Emory University Center for AIDS research [P30AI050409], and Atlanta Clinical and Translational Sciences Institute [KLR2TR000455, UL1TR000454]).
DISCLAIMER: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the U.S. Centers for Disease Control and Prevention or the Department of Health and Human Services.

Keywords: Female reproductive tract; HIV risk-factors; Macaque models; Menstrual cycle

DOI: https://doi.org/10.1016/j.ebiom.2021.103472