Universität zu Köln

Schramm, Michael, Wiegmann, Katja, Schramm, Sandra, Gluschko, Alexander, Herb, Marc ORCID: 0000-0002-7533-0288, Utermoehlen, Olaf and Kroenke, Martin (2014). Riboflavin (vitamin B2) deficiency impairs NADPH oxidase 2 (Nox2) priming and defense against Listeria monocytogenes. Eur. J. Immunol., 44 (3). S. 728 - 742. HOBOKEN: WILEY. ISSN 1521-4141

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Abstract

Riboflavin, also known as vitamin B-2, is converted by riboflavin kinase (RFK) into flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential cofactors of dehydrogenases, reductases, and oxidases including the phagocytic NADPH oxidase 2 (Nox2). Riboflavin deficiency is common in young adults and elderly individuals, who are at the coincidental risk for listeriosis. To address the impact of acute riboflavin deficiency on host defense against Listeria monocytogenes (L.m.), we generated conditional RFK knockout (KO) strains of mice. Phagocyte-specific RFK KO impaired the capability of phagocytes to control intracellular L.m., which corresponded to a greater susceptibility of mice to in vivo challenge with L.m. The oxidative burst of RFK-deficient phagocytes in response to L.m. infection was significantly reduced. Mechanistically, TNF-induced priming of Nox2, which is needed for oxidative burst, was defective in RFK-deficient phagocytes. Lack of riboflavin in wild-type macrophages for only 6 h shut down TNF-induced, RFK-mediated de novo FMN/FAD generation, which was accompanied by diminished ROS production and impaired anti-listerial activity. Vice versa, ROS production by riboflavin-deprived macrophages was rapidly restored by riboflavin supplementation. Our results suggest that acute riboflavin deficiency immediately impairs priming of Nox2, which is of crucial relevance for an effective phagocytic immune response in vivo.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schramm, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiegmann, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Schramm, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Gluschko, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Herb, Marc UNSPECIFIED orcid.org/0000-0002-7533-0288 UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-445276
DOI:	10.1002/eji.201343940
Journal or Publication Title:	Eur. J. Immunol.
Volume:	44
Number:	3
Page Range:	S. 728 - 742
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1521-4141
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REACTIVE OXYGEN; ACTIVATION; FAMILY; FAD Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44527