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Infect Immun. 2019 Aug 26. pii: IAI.00088-19. doi: 10.1128/IAI.00088-19. [Epub ahead of print]

Leishmania infection induces macrophage VEGF-A production in a ARNT/HIF-dependent manner.

Author information

1
Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205 tweinkopff@uams.edu.
2
Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
3
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA pscott@vet.upenn.edu.

Abstract

Cutaneous leishmaniasis is characterized by vascular remodeling. Following infection with Leishmania parasites, the VEGF-A/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 macrophages are the predominant cell type expressing VEGF-A during L. major infection. Given Leishmania parasites activate HIF-1α and this transcription factor can drive VEGF-A expression, we analyzed the expression of HIF-1α during infection. We showed macrophages were also the major cell type expressing HIF-1α 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 a ARNT/HIF-dependent manner and suggest that ARNT/HIF signaling may limit inflammation by promoting VEGF-A production and thus lymphangiogenesis during infection.

PMID:
31451620
DOI:
10.1128/IAI.00088-19

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