title: Myeloid Cell-Derived HIF-1α Promotes Control of Leishmania major.
abstract: Hypoxia-inducible factor-1α (HIF-1α), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. However, whether and to what extent HIF-1α expressed by myeloid cells contributes to the innate immune response against Leishmania major parasites is unknown. We observed that Leishmania-infected humans and L. major-infected C57BL/6 mice exhibited substantial amounts of HIF-1α in acute cutaneous lesions. In vitro, HIF-1α was required for leishmanicidal activity and high-level NO production by IFN-γ/LPS-activated macrophages. Mice deficient for HIF-1α in their myeloid cell compartment had a more severe clinical course of infection and increased parasite burden in the skin lesions compared with wild-type controls. These findings were paralleled by reduced expression of type 2 NO synthase by lesional CD11b+cells. Together, these data illustrate that HIF-1α is required for optimal innate leishmanicidal immune responses and, thereby, contributes to the cure of cutaneous leishmaniasis.
authors: Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany.
authors: Valentin
authors: 0000-0001-7784-8753
authors: V
authors: Schatz
authors: Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany.
authors: Yannic
authors: 0000-0002-8679-4862
authors: Y
authors: Strüssmann
authors: Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie, und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors: Alexander
authors: A
authors: Mahnke
authors: Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors: Gunnar
authors: G
authors: Schley
authors: Medizinische Klinik 1, Gastroenterologie, Pneumologie und Endokrinologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors: Maximilian
authors: M
authors: Waldner
authors: Institute of Immunology, University of Regensburg, 93053 Regensburg, Germany.
authors: Uwe
authors: 0000-0002-6281-4005
authors: U
authors: Ritter
authors: Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany.
authors: Jens
authors: 0000-0001-9880-7897
authors: J
authors: Wild
authors: Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors: Carsten
authors: C
authors: Willam
authors: Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, Germany; and.
authors: Nathalie
authors: 0000-0002-0822-2180
authors: N
authors: Dehne
authors: Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, Germany; and.
authors: Bernhard
authors: B
authors: Brüne
authors: Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.
authors: Jennifer M
authors: JM
authors: McNiff
authors: Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.
authors: Oscar R
authors: OR
authors: Colegio
authors: Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie, und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors: Christian
authors: C
authors: Bogdan
authors: Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany; jonathan.jantsch@ukr.de.
authors: Jonathan
authors: J
authors: Jantsch
mesh_terms: D000818:Animals; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D059208:Parasite Load; D012867:Skin / Q000469:parasitology* / Q000473:pathology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase