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https://www.arca.fiocruz.br/handle/icict/43834
DECIDUAL NK CELLS TRANSFER GRANULYSIN TO SELECTIVELY KILL BACTERIA IN TROPHOBLASTS
granulysin
maternal-fetal tolerance
extravillous trophoblast
Listeria monocytogenes
pregnancy
nanotube
cytotoxic granule
Author
Affilliation
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Department of Stem Cell and Regenerative Biology. Harvard University. Cambridge, MA, USA/PhD Programme in Experimental Biology and Biomedicine. Center for Neurosciences and Cell Biology. University of Coimbra. Coimbra, Portugal/Department of Pharmacy. University of Kota. Kota, Rajasthan, India
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Department of Pulmonary Immunology. Center for Biomedical Research. The University of Texas Health Science Center at Tyler. Tyler, TX, USA/Department of Pharmacy. University of Kota. Kota, Rajasthan, India
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, /Present address: Vaccine and Immunotherapy Center. The Wistar Institute. Philadelphia, PA /Division of Immunobiology and Center for Inflammation and Tolerance. Cincinnati Children’s Hospital, and Department of Pediatrics. University of Cincinnati College of Medicine.Cincinnati, OH, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA/ Fundacão Oswaldo Cruz. Instituto Rene ́Rachou. Belo Horizonte, MG, Brazil
Department of Stem Cell and Regenerative Biology. Harvard University. Cambridge, MA, USA/Institute for Research and Innovation in Health (i3S). University of Porto. Porto, Portugal
Department of Stem Cell and Regenerative Biology. Harvard University. Cambridge, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Department of Pulmonary Immunology. Center for Biomedical Research. The University of Texas Health Science Center at Tyler. Tyler, TX, USA/Department of Pharmacy. University of Kota. Kota, Rajasthan, India
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, /Present address: Vaccine and Immunotherapy Center. The Wistar Institute. Philadelphia, PA /Division of Immunobiology and Center for Inflammation and Tolerance. Cincinnati Children’s Hospital, and Department of Pediatrics. University of Cincinnati College of Medicine.Cincinnati, OH, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA/ Fundacão Oswaldo Cruz. Instituto Rene ́Rachou. Belo Horizonte, MG, Brazil
Department of Stem Cell and Regenerative Biology. Harvard University. Cambridge, MA, USA/Institute for Research and Innovation in Health (i3S). University of Porto. Porto, Portugal
Department of Stem Cell and Regenerative Biology. Harvard University. Cambridge, MA, USA
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA
Abstract
Maternal decidual NK (dNK) cells promote placentation, but how they protect against placental infection while maintaining fetal tolerance is unclear. Here we show that human dNK cells highly express the antimicrobial peptide granulysin (GNLY) and selectively transfer it via nanotubes to extravillous trophoblasts to kill intracellular Listeria monocytogenes (Lm) without killing the trophoblast. Transfer of GNLY, but not other cell death-inducing cytotoxic granule proteins, strongly inhibits Lm in human placental cultures and in mouse and human trophoblast cell lines. Placental and fetal Lm loads are lower and pregnancy success is greatly improved in pregnant Lm-infected GNLY-transgenic mice than in wild-type mice that lack GNLY. This immune defense is not restricted to pregnancy; peripheral NK (pNK) cells also transfer GNLY to kill bacteria in macrophages and dendritic cells without killing the host cell. Nanotube transfer of GNLY allows dNK to protect against infection while leaving the maternal-fetal barrier intact.
Keywords
decidual NK cellsgranulysin
maternal-fetal tolerance
extravillous trophoblast
Listeria monocytogenes
pregnancy
nanotube
cytotoxic granule
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