Neutrophil elastase promotes Leishmania donovani infection via interferon‐β

• DOI: 10.1096/fj.201900524r
• Publication Date: 2019-07-09T02:55:24Z
• Authors: Bruna T. Dias; Karina Luisa Dias...; Joseane P. Godinho; Marilia S. Faria; Teresa Calegari-S...; Maowia M. Mukhtar; Ulisses Lopes; Jeremy C. Mottram; Ana Paula C. A. Lima
• Keywords: Mice, Knockout; 0303 health sciences; Research; Macrophages; Protozoan Proteins; Interferon-beta; Toll-Like Receptor 2; 3. Good health; Animals, Genetically Modified; Mice, Inbred C57BL; Toll-Like Receptor 4; Mice; 03 medical and health sciences; Animals; Leishmaniasis, Visceral; Leukocyte Elastase; Leishmania donovani

Visceral leishmaniasis is a deadly illness caused by Leishmania donovani that provokes liver and spleen inflammation tissue destruction. In cutaneous leishmaniasis, the protein of L. major, named inhibitor serine peptidases (ISP) 2, inactivates neutrophil elastase (NE) present at macrophage surface, resulting in blockade TLR4 activation, prevention TNF-α* IFN-β production, parasite survival. We report poor intracellular growth macrophages from knockout mice for NE (ela−/−), TLR4, or TLR2. colocalized with parasitophorous vacuole. Parasite load ela−/− were reduced accompanied increased NO decreased TGF-β production. Expression ISP2 was not detected donovani, transgenic line constitutively expressing ISP2, displayed burden mice. Infected significantly lower mRNA than background macrophages, fully restored exogenous IFN-β. propose utilizes host NE-TLR machinery to induce necessary survival during early infection. Low absent expression preserve activation pathway.—Dias, B. T., Dias-Teixeira, K. L., Godinho, J. P., Faria, M. S., Calegari-Silva, Mukhtar, M., Lopes, U. G., Mottram, C., Lima, A. P. C. Neutrophil promotes infection via interferon-β. FASEB 33,10794–10807 (2019). www.fasebj.org