NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection

Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an important family of catalytic enzymes that generate reactive oxygen species (ROS), which mediate the regulation of diverse cellular functions. Although phagocyte Nox2/gp91phox is closely associated with the activation...

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Autores principales:	Ji Hye Kim, Jina Lee, Su-Jin Bae, Yeeun Kim, Byung-Joon Park, Jae-Won Choi, Jaeyul Kwon, Guang-Ho Cha, Heon Jong Yoo, Eun-Kyeong Jo, Yun Soo Bae, Young-Ha Lee, Jae-Min Yuk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4283dbd78b614c17a4ad3a03b5ead2b0
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spelling	oai:doaj.org-article:4283dbd78b614c17a4ad3a03b5ead2b02021-12-02T12:30:11ZNADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection10.1038/s41598-017-06610-42045-2322https://doaj.org/article/4283dbd78b614c17a4ad3a03b5ead2b02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06610-4https://doaj.org/toc/2045-2322Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an important family of catalytic enzymes that generate reactive oxygen species (ROS), which mediate the regulation of diverse cellular functions. Although phagocyte Nox2/gp91phox is closely associated with the activation of host innate immune responses, the roles of Nox family protein during Toxoplasma gondii (T. gondii) infection have not been fully investigated. Here, we found that T. gondii-mediated ROS production was required for the upregulation of macrophage migration inhibitory factor (MIF) mRNA and protein levels via activation of mitogen-activated protein kinase and nuclear factor-κB signaling in macrophages. Interestingly, MIF knockdown led to a significant increase in the survival of intracellular T. gondii in bone marrow-derived macrophages (BMDMs). Moreover, Nox4 deficiency, but not Nox2/gp91phox and the cytosolic subunit p47phox, resulted in enhanced survival of the intracellular T. gondii RH strain and impaired expression of T. gondii-mediated MIF in BMDMs. Additionally, Nox4-deficient mice showed increased susceptibility to virulent RH strain infection and increased cyst burden in brain tissues and low levels of MIF expression following infection with the avirulent ME49 strain. Collectively, our findings indicate that Nox4-mediated ROS generation plays a central role in MIF production and resistance to T. gondii infection.Ji Hye KimJina LeeSu-Jin BaeYeeun KimByung-Joon ParkJae-Won ChoiJaeyul KwonGuang-Ho ChaHeon Jong YooEun-Kyeong JoYun Soo BaeYoung-Ha LeeJae-Min YukNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ji Hye Kim Jina Lee Su-Jin Bae Yeeun Kim Byung-Joon Park Jae-Won Choi Jaeyul Kwon Guang-Ho Cha Heon Jong Yoo Eun-Kyeong Jo Yun Soo Bae Young-Ha Lee Jae-Min Yuk NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection
description	Abstract Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an important family of catalytic enzymes that generate reactive oxygen species (ROS), which mediate the regulation of diverse cellular functions. Although phagocyte Nox2/gp91phox is closely associated with the activation of host innate immune responses, the roles of Nox family protein during Toxoplasma gondii (T. gondii) infection have not been fully investigated. Here, we found that T. gondii-mediated ROS production was required for the upregulation of macrophage migration inhibitory factor (MIF) mRNA and protein levels via activation of mitogen-activated protein kinase and nuclear factor-κB signaling in macrophages. Interestingly, MIF knockdown led to a significant increase in the survival of intracellular T. gondii in bone marrow-derived macrophages (BMDMs). Moreover, Nox4 deficiency, but not Nox2/gp91phox and the cytosolic subunit p47phox, resulted in enhanced survival of the intracellular T. gondii RH strain and impaired expression of T. gondii-mediated MIF in BMDMs. Additionally, Nox4-deficient mice showed increased susceptibility to virulent RH strain infection and increased cyst burden in brain tissues and low levels of MIF expression following infection with the avirulent ME49 strain. Collectively, our findings indicate that Nox4-mediated ROS generation plays a central role in MIF production and resistance to T. gondii infection.
format	article
author	Ji Hye Kim Jina Lee Su-Jin Bae Yeeun Kim Byung-Joon Park Jae-Won Choi Jaeyul Kwon Guang-Ho Cha Heon Jong Yoo Eun-Kyeong Jo Yun Soo Bae Young-Ha Lee Jae-Min Yuk
author_facet	Ji Hye Kim Jina Lee Su-Jin Bae Yeeun Kim Byung-Joon Park Jae-Won Choi Jaeyul Kwon Guang-Ho Cha Heon Jong Yoo Eun-Kyeong Jo Yun Soo Bae Young-Ha Lee Jae-Min Yuk
author_sort	Ji Hye Kim
title	NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection
title_short	NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection
title_full	NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection
title_fullStr	NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection
title_full_unstemmed	NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection
title_sort	nadph oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against toxoplasma gondii infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4283dbd78b614c17a4ad3a03b5ead2b0
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NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection

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