Myeloid Cell-Derived HIF-1? Promotes Control of Leishmania major.

ABSTRACT: Hypoxia-inducible factor-1? (HIF-1?), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. However, whether and to what extent HIF-1? 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-1? in acute cutaneous lesions. In vitro, HIF-1? was required for leishmanicidal activity and high-level NO production by IFN-?/LPS-activated macrophages. Mice deficient for HIF-1? 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? is required for optimal innate leishmanicidal immune responses and, thereby, contributes to the cure of cutaneous leishmaniasis.

SUBMITTER: Schatz V 

PROVIDER: S-EPMC7249608 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature