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Medientyp:
E-Artikel
Titel:
Myeloid Cell–Derived HIF-1α Promotes Control of Leishmania major
Beteiligte:
Schatz, Valentin;
Strüssmann, Yannic;
Mahnke, Alexander;
Schley, Gunnar;
Waldner, Maximilian;
Ritter, Uwe;
Wild, Jens;
Willam, Carsten;
Dehne, Nathalie;
Brüne, Bernhard;
McNiff, Jennifer M.;
Colegio, Oscar R.;
Bogdan, Christian;
Jantsch, Jonathan
Erschienen:
The American Association of Immunologists, 2016
Erschienen in:
The Journal of Immunology, 197 (2016) 10, Seite 4034-4041
Sprache:
Englisch
DOI:
10.4049/jimmunol.1601080
ISSN:
0022-1767;
1550-6606
Entstehung:
Anmerkungen:
Beschreibung:
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.