biostudies-literatureDias BTConselho Nacional de Desenvolvimento Científico e TecnológicoMedical Research CouncilFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro10794-10807https://www.ebi.ac.uk/biostudies/studies/S-EPMC6766642biostudies-literatureUnknown33(10)Visceral leishmaniasis is a deadly illness caused by <i>Leishmania donovani</i> that provokes liver and spleen inflammation and tissue destruction. In cutaneous leishmaniasis, the protein of <i>L. major</i>, 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 <i>L. donovani</i> in macrophages from knockout mice for NE (<i>ela</i>^-/-), TLR4, or TLR2. NE and TLR4 colocalized with the parasite in the parasitophorous vacuole. Parasite load in the liver and spleen of <i>ela</i>^-/- mice were reduced and accompanied by increased NO and decreased TGF-β production. ExpFASEB journal : official publication of the Federation of American Societies for Experimental BiologyNeutrophil elastase promotes <i>Leishmania donovani</i> infection <i>via</i> interferon-β.PMC6766642MR/N017269/1MR/P027989/1Mukhtar MMGodinho JPMottram JCLima APCACalegari-Silva TDias BTFaria MSDias-Teixeira KLLopes UfalseNeutrophil elastase promotes <i>Leishmania donovani</i> infection <i>via</i> interferon-β.Visceral leishmaniasis is a deadly illness caused by <i>Leishmania donovani</i> that provokes liver and spleen inflammation and tissue destruction. In cutaneous leishmaniasis, the protein of <i>L. major</i>, 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 <i>L. donovani</i> in macrophages from knockout mice for NE (<i>ela</i>^-/-), TLR4, or TLR2. NE and TLR4 colocalized with the parasite in the parasitophorous vacuole. Parasite load in the liver and spleen of <i>ela</i>^-/- mice were reduced and accompanied by increased NO and decreased TGF-β production. Exp2019-01-01T00:00:00Z2019 Oct2025-04-21T23:28:05.406Z2019-10-11T07:12:51ZS-EPMC67666423128475510.1096/fj.201900524R