A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells

Abstract Phagocytosis of microbial pathogens, dying or dead cells, and cell debris is essential to maintain tissue homeostasis. Impairment of these processes is associated with autoimmunity, developmental defects and toxic protein accumulation. However, the underlying molecular mechanisms of phagocy...

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Autores principales:	Benjamin Lindner, Eva Martin, Monika Steininger, Aleksandra Bundalo, Martin Lenter, Johannes Zuber, Michael Schuler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2d507b2b5d447639ff1bed120983bd7
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spelling	oai:doaj.org-article:a2d507b2b5d447639ff1bed120983bd72021-12-02T17:45:11ZA genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells10.1038/s41598-021-92332-72045-2322https://doaj.org/article/a2d507b2b5d447639ff1bed120983bd72021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92332-7https://doaj.org/toc/2045-2322Abstract Phagocytosis of microbial pathogens, dying or dead cells, and cell debris is essential to maintain tissue homeostasis. Impairment of these processes is associated with autoimmunity, developmental defects and toxic protein accumulation. However, the underlying molecular mechanisms of phagocytosis remain incompletely understood. Here, we performed a genome-wide CRISPR knockout screen to systematically identify regulators involved in phagocytosis of Staphylococcus (S.) aureus by human monocytic THP-1 cells. The screen identified 75 hits including known regulators of phagocytosis, e.g. members of the actin cytoskeleton regulation Arp2/3 and WAVE complexes, as well as genes previously not associated with phagocytosis. These novel genes are involved in translational control (EIF5A and DHPS) and the UDP glycosylation pathway (SLC35A2, SLC35A3, UGCG and UXS1) and were further validated by single gene knockout experiments. Whereas the knockout of EIF5A and DHPS impaired phagocytosis, knocking out SLC35A2, SLC35A3, UGCG and UXS1 resulted in increased phagocytosis. In addition to S. aureus phagocytosis, the above described genes also modulate phagocytosis of Escherichia coli and yeast-derived zymosan A. In summary, we identified both known and unknown genetic regulators of phagocytosis, the latter providing a valuable resource for future studies dissecting the underlying molecular and cellular mechanisms and their role in human disease.Benjamin LindnerEva MartinMonika SteiningerAleksandra BundaloMartin LenterJohannes ZuberMichael SchulerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Lindner Eva Martin Monika Steininger Aleksandra Bundalo Martin Lenter Johannes Zuber Michael Schuler A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells
description	Abstract Phagocytosis of microbial pathogens, dying or dead cells, and cell debris is essential to maintain tissue homeostasis. Impairment of these processes is associated with autoimmunity, developmental defects and toxic protein accumulation. However, the underlying molecular mechanisms of phagocytosis remain incompletely understood. Here, we performed a genome-wide CRISPR knockout screen to systematically identify regulators involved in phagocytosis of Staphylococcus (S.) aureus by human monocytic THP-1 cells. The screen identified 75 hits including known regulators of phagocytosis, e.g. members of the actin cytoskeleton regulation Arp2/3 and WAVE complexes, as well as genes previously not associated with phagocytosis. These novel genes are involved in translational control (EIF5A and DHPS) and the UDP glycosylation pathway (SLC35A2, SLC35A3, UGCG and UXS1) and were further validated by single gene knockout experiments. Whereas the knockout of EIF5A and DHPS impaired phagocytosis, knocking out SLC35A2, SLC35A3, UGCG and UXS1 resulted in increased phagocytosis. In addition to S. aureus phagocytosis, the above described genes also modulate phagocytosis of Escherichia coli and yeast-derived zymosan A. In summary, we identified both known and unknown genetic regulators of phagocytosis, the latter providing a valuable resource for future studies dissecting the underlying molecular and cellular mechanisms and their role in human disease.
format	article
author	Benjamin Lindner Eva Martin Monika Steininger Aleksandra Bundalo Martin Lenter Johannes Zuber Michael Schuler
author_facet	Benjamin Lindner Eva Martin Monika Steininger Aleksandra Bundalo Martin Lenter Johannes Zuber Michael Schuler
author_sort	Benjamin Lindner
title	A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells
title_short	A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells
title_full	A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells
title_fullStr	A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells
title_full_unstemmed	A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells
title_sort	genome-wide crispr/cas9 screen to identify phagocytosis modulators in monocytic thp-1 cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a2d507b2b5d447639ff1bed120983bd7
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A genome-wide CRISPR/Cas9 screen to identify phagocytosis modulators in monocytic THP-1 cells

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