By the same authors

From the same journal

NEUTROPHIL ELASTASE PROMOTES Leishmania donovani INFECTION VIA INTERFERON beta

Research output: Contribution to journalArticle

Published copy (DOI)

Author(s)

  • Bruna Torres Dias
  • Karina L. Teixeira
  • Joseane P. Godinho
  • Marilia S. Faria
  • Teresa Calegari-Silva
  • Maowia M. Mukhtar
  • Ulisses Gazos Lopes
  • Jeremy Charles Mottram
  • Ana Paula C.A. Lima

Department/unit(s)

Publication details

JournalThe FASEB Journal
DateAccepted/In press - 4 Jun 2019
DateE-pub ahead of print (current) - 5 Jul 2019
Early online date5/07/19
Original languageEnglish

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 (ISP2) inactivates neutrophil elastase (NE) present at the macrophage surface, resulting in blockade of TLR4 activation, prevention of TNF and IFN production and parasite survival. We report poor intracellular growth of L. donovani in macrophages from knock-out mice for NE (ela-/-), TLR4 or TLR2. NE and TLR4 co-localized with the parasite in the parasitophorous vacuole. Parasite load in the liver and spleen of ela-/- mice were reduced and accompanied by increased nitric oxide and decreased TGF production. Expression of ISP2 was not detected in L. donovani and a transgenic line constitutively expressing ISP2, displayed poor intracellular growth in macrophages and decreased burden in mice. Infected ela-/- macrophages displayed significantly lower IFN mRNA than background mice macrophages and the intracellular growth of was fully restored by exogenous IFN. We propose that L. donovani utilizes the host NE-TLR machinery to induce IFN necessary for parasite survival/growth during early infection. Low or absent expression of parasite ISP2 in L. donovani is necessary to preserve the activation of the NE-TLR pathway.

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations