| First Author | Weinkopff T | Year | 2019 |
| Journal | Infect Immun | Volume | 87 |
| Issue | 11 | PubMed ID | 31451620 |
| Mgi Jnum | J:292819 | Mgi Id | MGI:6435237 |
| Doi | 10.1128/IAI.00088-19 | Citation | Weinkopff T, et al. (2019) Leishmania Infection Induces Macrophage Vascular Endothelial Growth Factor A Production in an ARNT/HIF-Dependent Manner. Infect Immun 87(11) |
| abstractText | Cutaneous leishmaniasis is characterized by vascular remodeling. Following infection with Leishmania parasites, the vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 (VEGFR-2) signaling pathway mediates lymphangiogenesis, which is critical for lesion resolution. Therefore, we investigated the cellular and molecular mediators involved in VEGF-A/VEGFR-2 signaling using a murine model of infection. We found that macrophages are the predominant cell type expressing VEGF-A during Leishmania major infection. Given that Leishmania parasites activate hypoxia-inducible factor 1alpha (HIF-1alpha) and this transcription factor can drive VEGF-A expression, we analyzed the expression of HIF-1alpha during infection. We showed that macrophages were also the major cell type expressing HIF-1alpha during infection and that infection-induced VEGF-A production is mediated by ARNT/HIF activation. Furthermore, mice deficient in myeloid ARNT/HIF signaling exhibited larger lesions without differences in parasite numbers. These data show that L. major infection induces macrophage VEGF-A production in an ARNT/HIF-dependent manner and suggest that ARNT/HIF signaling may limit inflammation by promoting VEGF-A production and, thus, lymphangiogenesis during infection. |
