Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila

Abstract Drosophila immune deficiency (IMD) pathway is similar to the human tumor necrosis factor receptor (TNFR) signaling pathway and is preferentially activated by Gram-negative bacterial infection. Recent studies highlighted the importance of IMD pathway regulation as it is tightly controlled by...

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Autores principales:	Pragya Prakash, Arghyashree Roychowdhury-Sinha, Akira Goto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ec7c2b5051f4064ad48078c729a160b
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spelling	oai:doaj.org-article:2ec7c2b5051f4064ad48078c729a160b2021-12-02T16:23:42ZVerloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila10.1038/s41598-021-94973-02045-2322https://doaj.org/article/2ec7c2b5051f4064ad48078c729a160b2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94973-0https://doaj.org/toc/2045-2322Abstract Drosophila immune deficiency (IMD) pathway is similar to the human tumor necrosis factor receptor (TNFR) signaling pathway and is preferentially activated by Gram-negative bacterial infection. Recent studies highlighted the importance of IMD pathway regulation as it is tightly controlled by numbers of negative regulators at multiple levels. Here, we report a new negative regulator of the IMD pathway, Verloren (Velo). Silencing of Velo led to constitutive expression of the IMD pathway dependent antimicrobial peptides (AMPs), and Escherichia coli stimulation further enhanced the AMP expression. Epistatic analysis indicated that Velo knock-down mediated AMP upregulation is dependent on the canonical members of the IMD pathway. The immune fluorescent study using overexpression constructs revealed that Velo resides both in the nucleus and cytoplasm, but the majority (~ 75%) is localized in the nucleus. We also observed from in vivo analysis that Velo knock-down flies exhibit significant upregulation of the AMP expression and reduced bacterial load. Survival experiments showed that Velo knock-down flies have a short lifespan and are susceptible to the infection of pathogenic Gram-negative bacteria, P. aeruginosa. Taken together, these data suggest that Velo is an additional new negative regulator of the IMD pathway, possibly acting in both the nucleus and cytoplasm.Pragya PrakashArghyashree Roychowdhury-SinhaAkira GotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pragya Prakash Arghyashree Roychowdhury-Sinha Akira Goto Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila
description	Abstract Drosophila immune deficiency (IMD) pathway is similar to the human tumor necrosis factor receptor (TNFR) signaling pathway and is preferentially activated by Gram-negative bacterial infection. Recent studies highlighted the importance of IMD pathway regulation as it is tightly controlled by numbers of negative regulators at multiple levels. Here, we report a new negative regulator of the IMD pathway, Verloren (Velo). Silencing of Velo led to constitutive expression of the IMD pathway dependent antimicrobial peptides (AMPs), and Escherichia coli stimulation further enhanced the AMP expression. Epistatic analysis indicated that Velo knock-down mediated AMP upregulation is dependent on the canonical members of the IMD pathway. The immune fluorescent study using overexpression constructs revealed that Velo resides both in the nucleus and cytoplasm, but the majority (~ 75%) is localized in the nucleus. We also observed from in vivo analysis that Velo knock-down flies exhibit significant upregulation of the AMP expression and reduced bacterial load. Survival experiments showed that Velo knock-down flies have a short lifespan and are susceptible to the infection of pathogenic Gram-negative bacteria, P. aeruginosa. Taken together, these data suggest that Velo is an additional new negative regulator of the IMD pathway, possibly acting in both the nucleus and cytoplasm.
format	article
author	Pragya Prakash Arghyashree Roychowdhury-Sinha Akira Goto
author_facet	Pragya Prakash Arghyashree Roychowdhury-Sinha Akira Goto
author_sort	Pragya Prakash
title	Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila
title_short	Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila
title_full	Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila
title_fullStr	Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila
title_full_unstemmed	Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila
title_sort	verloren negatively regulates the expression of imd pathway dependent antimicrobial peptides in drosophila
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2ec7c2b5051f4064ad48078c729a160b
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Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila

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