| First Author | Hammami A | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 3500 |
| PubMed ID | 29472618 | Mgi Jnum | J:263072 |
| Mgi Id | MGI:6162872 | Doi | 10.1038/s41598-018-21891-z |
| Citation | Hammami A, et al. (2018) HIF-1alpha hampers dendritic cell function and Th1 generation during chronic visceral leishmaniasis. Sci Rep 8(1):3500 |
| abstractText | Inflammation, although responsible for controlling infection, is often associated with the pathogenesis of chronic diseases. Leishmania donovani, the causative agent of visceral leishmaniasis, induces a strong inflammatory response that leads to splenomegaly and ultimately immune suppression. Inflamed tissues are typically characterized by low levels of oxygen, a microenvironment that triggers the hypoxia-inducible transcription factor 1alpha (HIF-1alpha). Although HIF-1alpha plays an integral role in dendritic cell function, its involvement in the generation of protective Th1 responses against Leishmania has not yet been studied. Here we demonstrate that HIF-1alpha inhibits IL-12 production in dendritic cells, limiting therefore Th1 cell development. Indeed, depletion of HIF-1alpha in CD11c(+) cells resulted in higher and sustained expression of IL-12 and complete abrogation of IL-10. Moreover, CD11c-specific HIF-1alpha-deficient mice showed higher frequencies of IFN-gamma-producing CD4 T cells in the spleen and bone marrow and, consequently, a significantly reduced parasite burden in both organs. Taken together, our results suggest that HIF-1alpha expression in dendritic cells largely contributes to the establishment of persistent Leishmania infection and may therefore represent a possible therapeutic target. |
