Granulysin-high decidual NK cells in macaques and humans share signatures of immune defense

Nina Salinger Prasanphanich; Giulia Protti; Monica Cappelletti; Feiyang Ma; Neema Pithia; Angel Dasenbrock; Jerzy Stanek; Claire A Chougnet; Suhas G Kallapur; Matteo Pellegrini; Tamara Tilburgs; Pietro Presicce

doi:10.1016/j.celrep.2025.115943

Granulysin-high decidual NK cells in macaques and humans share signatures of immune defense

Cell Rep. 2025 Jul 8;44(7):115943. doi: 10.1016/j.celrep.2025.115943. Online ahead of print.

Authors

Affiliations

¹ Division of Infectious Disease, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
² Department of Molecular, Cell and Developmental Biology Medicine at the University of California, Los Angeles, 610 Charles E. Young Dr. S, Los Angeles, CA 90095, USA; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
³ Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, Los Angeles, CA 90095, USA.
⁴ Department of Molecular, Cell and Developmental Biology Medicine at the University of California, Los Angeles, 610 Charles E. Young Dr. S, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences - Collaboratory at the University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Cell and Developmental Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
⁵ Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁷ Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
⁸ Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
⁹ Department of Molecular, Cell and Developmental Biology Medicine at the University of California, Los Angeles, 610 Charles E. Young Dr. S, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences - Collaboratory at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁰ Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: tamara.tilburgs@cchmc.org.
¹¹ Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ppresicce@mednet.ucla.edu.

PMID: 40638390
DOI: 10.1016/j.celrep.2025.115943

Abstract

Decidual natural killer cells (dNKs) are key immune effector cells at the maternal-fetal interface. dNKs utilize the antimicrobial peptide granulysin (GNLY) to kill bacteria without killing infected trophoblasts. Since rodents lack the GNLY gene, the in vivo biology of GNLY expression by dNKs and their role during intra-uterine infection (IUI) is not well understood. Here, we defined dNK GNLY expression in placental membranes in a rhesus macaque model of IUI and compared it with human acute chorioamnionitis (ACA). GNLY-high dNKs of both species shared conserved transcriptional and protein signatures of antimicrobial defense and immunoregulation. Moreover, GNLY-high dNKs responded to inflammation and infection by increasing their cytotoxic, cytokine, and inflammatory signatures. Thus, high GNLY expression defines a unique dNK type with active roles in immune defense. Defining the regulatory networks of GNLY expression by dNKs and their unique mechanisms of infection control will generate therapeutic opportunities to enhance immunity and reduce IUI-related pregnancy complications.

Keywords: CP: Immunology; Intra-uterine infection; chorioamnionitis; cytotoxicity; dNK; decidua; granulysin; innate immunity; natural killer cells; placenta; pregnancy.