Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis

Abstract How multicellular organisms maintain immune homeostasis across various organs and cell types is an outstanding question in immune biology and cell signaling. In Drosophila, blood cells (hemocytes) respond to local and systemic cues to mount an immune response. While endosomal regulation of...

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Autores principales:	Rohan J. Khadilkar, Arindam Ray, D. R. Chetan, Arghyashree RoyChowdhury Sinha, Srivathsa S. Magadi, Vani Kulkarni, Maneesha S. Inamdar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/82faed248be543d8ac6221297f97b446
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spelling	oai:doaj.org-article:82faed248be543d8ac6221297f97b4462021-12-02T16:07:01ZDifferential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis10.1038/s41598-017-00118-72045-2322https://doaj.org/article/82faed248be543d8ac6221297f97b4462017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00118-7https://doaj.org/toc/2045-2322Abstract How multicellular organisms maintain immune homeostasis across various organs and cell types is an outstanding question in immune biology and cell signaling. In Drosophila, blood cells (hemocytes) respond to local and systemic cues to mount an immune response. While endosomal regulation of Drosophila hematopoiesis is reported, the role of endosomal proteins in cellular and humoral immunity is not well-studied. Here we demonstrate a functional role for endosomal proteins in immune homeostasis. We show that the ubiquitous trafficking protein ADP Ribosylation Factor 1 (ARF1) and the hemocyte-specific endosomal regulator Asrij differentially regulate humoral immunity. Asrij and ARF1 play an important role in regulating the cellular immune response by controlling the crystal cell melanization and phenoloxidase activity. ARF1 and Asrij mutants show reduced survival and lifespan upon infection, indicating perturbed immune homeostasis. The ARF1-Asrij axis suppresses the Toll pathway anti-microbial peptides (AMPs) by regulating ubiquitination of the inhibitor Cactus. The Imd pathway is inversely regulated- while ARF1 suppresses AMPs, Asrij is essential for AMP production. Several immune mutants have reduced Asrij expression, suggesting that Asrij co-ordinates with these pathways to regulate the immune response. Our study highlights the role of endosomal proteins in modulating the immune response by maintaining the balance of AMP production. Similar mechanisms can now be tested in mammalian hematopoiesis and immunity.Rohan J. KhadilkarArindam RayD. R. ChetanArghyashree RoyChowdhury SinhaSrivathsa S. MagadiVani KulkarniManeesha S. InamdarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rohan J. Khadilkar Arindam Ray D. R. Chetan Arghyashree RoyChowdhury Sinha Srivathsa S. Magadi Vani Kulkarni Maneesha S. Inamdar Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis
description	Abstract How multicellular organisms maintain immune homeostasis across various organs and cell types is an outstanding question in immune biology and cell signaling. In Drosophila, blood cells (hemocytes) respond to local and systemic cues to mount an immune response. While endosomal regulation of Drosophila hematopoiesis is reported, the role of endosomal proteins in cellular and humoral immunity is not well-studied. Here we demonstrate a functional role for endosomal proteins in immune homeostasis. We show that the ubiquitous trafficking protein ADP Ribosylation Factor 1 (ARF1) and the hemocyte-specific endosomal regulator Asrij differentially regulate humoral immunity. Asrij and ARF1 play an important role in regulating the cellular immune response by controlling the crystal cell melanization and phenoloxidase activity. ARF1 and Asrij mutants show reduced survival and lifespan upon infection, indicating perturbed immune homeostasis. The ARF1-Asrij axis suppresses the Toll pathway anti-microbial peptides (AMPs) by regulating ubiquitination of the inhibitor Cactus. The Imd pathway is inversely regulated- while ARF1 suppresses AMPs, Asrij is essential for AMP production. Several immune mutants have reduced Asrij expression, suggesting that Asrij co-ordinates with these pathways to regulate the immune response. Our study highlights the role of endosomal proteins in modulating the immune response by maintaining the balance of AMP production. Similar mechanisms can now be tested in mammalian hematopoiesis and immunity.
format	article
author	Rohan J. Khadilkar Arindam Ray D. R. Chetan Arghyashree RoyChowdhury Sinha Srivathsa S. Magadi Vani Kulkarni Maneesha S. Inamdar
author_facet	Rohan J. Khadilkar Arindam Ray D. R. Chetan Arghyashree RoyChowdhury Sinha Srivathsa S. Magadi Vani Kulkarni Maneesha S. Inamdar
author_sort	Rohan J. Khadilkar
title	Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis
title_short	Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis
title_full	Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis
title_fullStr	Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis
title_full_unstemmed	Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis
title_sort	differential modulation of the cellular and humoral immune responses in drosophila is mediated by the endosomal arf1-asrij axis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/82faed248be543d8ac6221297f97b446
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Differential modulation of the cellular and humoral immune responses in Drosophila is mediated by the endosomal ARF1-Asrij axis

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