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GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18
by
Wagner, Andrew S.
, Huttenlocher, Anna
, Skala, Melissa C.
, Smith, Frances M.
, Bennin, David A.
, Votava, James A.
, Datta, Rupsa
, Zhao, Wenxuan
, Giese, Morgan A.
, Fan, Jing
, Keller, Nancy P.
in
Antifungal activity
/ Antimicrobial agents
/ Aspergillosis - immunology
/ Aspergillus fumigatus - immunology
/ Biology and Life Sciences
/ CD18 antigen
/ CD18 Antigens - genetics
/ CD18 Antigens - immunology
/ CD18 Antigens - metabolism
/ Cells, Cultured
/ Deletion
/ Development and progression
/ Fungi
/ Fungicides
/ GATA-1 protein
/ GATA1 Transcription Factor - deficiency
/ GATA1 Transcription Factor - genetics
/ GATA1 Transcription Factor - immunology
/ Genetic aspects
/ Glucan
/ Health aspects
/ Humans
/ Immunity
/ Induced Pluripotent Stem Cells - immunology
/ Integrins
/ Leukocytes (neutrophilic)
/ Medicine and Health Sciences
/ Metabolism
/ Mycoses
/ Neutrophils
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Pathogens
/ Pattern recognition
/ Pattern recognition receptors
/ Pentose
/ Pentose phosphate pathway
/ Physical Sciences
/ Pluripotency
/ Stem cells
/ Transcription factors
2025
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GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18
by
Wagner, Andrew S.
, Huttenlocher, Anna
, Skala, Melissa C.
, Smith, Frances M.
, Bennin, David A.
, Votava, James A.
, Datta, Rupsa
, Zhao, Wenxuan
, Giese, Morgan A.
, Fan, Jing
, Keller, Nancy P.
in
Antifungal activity
/ Antimicrobial agents
/ Aspergillosis - immunology
/ Aspergillus fumigatus - immunology
/ Biology and Life Sciences
/ CD18 antigen
/ CD18 Antigens - genetics
/ CD18 Antigens - immunology
/ CD18 Antigens - metabolism
/ Cells, Cultured
/ Deletion
/ Development and progression
/ Fungi
/ Fungicides
/ GATA-1 protein
/ GATA1 Transcription Factor - deficiency
/ GATA1 Transcription Factor - genetics
/ GATA1 Transcription Factor - immunology
/ Genetic aspects
/ Glucan
/ Health aspects
/ Humans
/ Immunity
/ Induced Pluripotent Stem Cells - immunology
/ Integrins
/ Leukocytes (neutrophilic)
/ Medicine and Health Sciences
/ Metabolism
/ Mycoses
/ Neutrophils
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Pathogens
/ Pattern recognition
/ Pattern recognition receptors
/ Pentose
/ Pentose phosphate pathway
/ Physical Sciences
/ Pluripotency
/ Stem cells
/ Transcription factors
2025
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GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18
by
Wagner, Andrew S.
, Huttenlocher, Anna
, Skala, Melissa C.
, Smith, Frances M.
, Bennin, David A.
, Votava, James A.
, Datta, Rupsa
, Zhao, Wenxuan
, Giese, Morgan A.
, Fan, Jing
, Keller, Nancy P.
in
Antifungal activity
/ Antimicrobial agents
/ Aspergillosis - immunology
/ Aspergillus fumigatus - immunology
/ Biology and Life Sciences
/ CD18 antigen
/ CD18 Antigens - genetics
/ CD18 Antigens - immunology
/ CD18 Antigens - metabolism
/ Cells, Cultured
/ Deletion
/ Development and progression
/ Fungi
/ Fungicides
/ GATA-1 protein
/ GATA1 Transcription Factor - deficiency
/ GATA1 Transcription Factor - genetics
/ GATA1 Transcription Factor - immunology
/ Genetic aspects
/ Glucan
/ Health aspects
/ Humans
/ Immunity
/ Induced Pluripotent Stem Cells - immunology
/ Integrins
/ Leukocytes (neutrophilic)
/ Medicine and Health Sciences
/ Metabolism
/ Mycoses
/ Neutrophils
/ Neutrophils - immunology
/ Neutrophils - metabolism
/ Pathogens
/ Pattern recognition
/ Pattern recognition receptors
/ Pentose
/ Pentose phosphate pathway
/ Physical Sciences
/ Pluripotency
/ Stem cells
/ Transcription factors
2025
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GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18
Journal Article
GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18
2025
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Overview
Neutrophils are critical for host defense against fungi. However, the short life span and lack of genetic tractability of primary human neutrophils has limited in vitro analysis of neutrophil-fungal interactions. Human induced pluripotent stem cell (iPSC)-derived neutrophils (iNeutrophils) provide a genetically tractable system to study host defense responses of human neutrophils. Here, we show that deletion of the transcription factor GATA1 from human iPSCs results in iNeutrophils with improved antifungal activity against Aspergillus fumigatus . GATA1-knockout (KO) iNeutrophils have increased maturation, antifungal pattern recognition receptor expression and have improved neutrophil effector functions compared to wild-type iNeutrophils. iNeutrophils also show a shift in their metabolism following stimulation with fungal β-glucan to the pentose phosphate pathway (PPP), similar to primary human neutrophils. Furthermore, we show that deletion of the integrin CD18 attenuates the ability of GATA1-KO iNeutrophils to kill A. fumigatus but is not necessary for the metabolic shift . Collectively, these findings support iNeutrophils as a robust system to study human neutrophil antifungal immunity and has identified specific roles for CD18 in the defense response .
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Aspergillus fumigatus - immunology
/ Deletion
/ Fungi
/ GATA1 Transcription Factor - deficiency
/ GATA1 Transcription Factor - genetics
/ GATA1 Transcription Factor - immunology
/ Glucan
/ Humans
/ Immunity
/ Induced Pluripotent Stem Cells - immunology
/ Medicine and Health Sciences
/ Mycoses
/ Pattern recognition receptors
/ Pentose
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