Schatz, Valentin and Strussmann, Yannic and Mahnke, Alexander and Schley, Gunnar and Waldner, Maximilian and Ritter, Uwe and Wild, Jens and Willam, Carsten and Dehne, Nathalie and Brune, Bernhard and McNiff, Jennifer M. and Colegio, Oscar R. and Bogdan, Christian and Jantsch, Jonathan (2016) Myeloid Cell-Derived HIF-1 alpha Promotes Control of Leishmania major. JOURNAL OF IMMUNOLOGY, 197 (10). pp. 4034-4041. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)Abstract
Hypoxia-inducible factor-1 alpha (HIF-1 alpha), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. However, whether and to what extent HIF-1 alpha expressed by myeloid cells contributes to the innate immune response against Leishmania major parasites is unknown. We observed that Leishmania-infected humans and L. majorinfected C57BL/6 mice exhibited substantial amounts of HIF-1 alpha in acute cutaneous lesions. In vitro, HIF-1 alpha was required for leishmanicidal activity and high-level NO production by IFN-gamma/LPS-activated macrophages. Mice deficient for HIF-1 alpha 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-1 alpha is required for optimal innate leishmanicidal immune responses and, thereby, contributes to the cure of cutaneous leishmaniasis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; BACTERICIDAL CAPACITY; TRANSCRIPTION FACTORS; RESPONSIVE ELEMENT; PROTOZOAN PARASITE; GENE-EXPRESSION; TUMOR-GROWTH; BALB/C MICE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Apr 2019 10:28 |
| Last Modified: | 12 Apr 2019 10:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3946 |
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