Neutrophil elastase promotes Leishmania donovani infection via interferon-β.

ABSTRACT: Visceral leishmaniasis is a deadly illness caused by Leishmania donovani that provokes liver and spleen inflammation and tissue destruction. In cutaneous leishmaniasis, the protein of L. major, named inhibitor of serine peptidases (ISP) 2, inactivates neutrophil elastase (NE) present at the macrophage surface, resulting in blockade of TLR4 activation, prevention of TNF-α and IFN-β production, and parasite survival. We report poor intracellular growth of L. donovani in macrophages from knockout mice for NE (ela^-/-), TLR4, or TLR2. NE and TLR4 colocalized with the parasite in the parasitophorous vacuole. Parasite load in the liver and spleen of ela^-/- mice were reduced and accompanied by increased NO and decreased TGF-β production. Exp

SUBMITTER: Dias BT 

PROVIDER: S-EPMC6766642 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature