DOI: 10.5061/dryad.tr4185n
title: Data from: Proteomic analysis reveals a predominant NFE2L2 (NRF2) signature in the ​canonical pathway and upstream regulator analysis of Leishmania-infected macrophages

description: CBA mice macrophages (MØ) control infection by Leishmania major and are
 susceptive to Leishmania amazonensis, suggesting that both parasite
 species induce distinct responses that play important roles in infection
 outcome. To evaluate the MØ responses to infection arising from these two
 Leishmania species, a proteomic study using a Multidimensional Protein
 Identification Technology (MudPIT) approach with liquid chromatography
 tandem mass spectrometry (LC-MS/MS) was carried out on CBA mice
 bone-marrow MØ (BMMØ). Following SEQUEST analysis, which revealed 2,838
 proteins detected in BMMØ, data mining approach found six proteins
 significantly associated with the tested conditions. To investigate their
 biological significance, enrichment analysis was performed using Ingenuity
 Pathway Analysis (IPA). A three steps IPA approach revealed 4 Canonical
 Pathways (CP) and 7 Upstream Transcriptional Factors (UTFs) strongly
 associated with the infection process. NRF2 signatures were present in
 both CPs and UTFs pathways. Proteins involved in iron metabolism, such as
 heme oxigenase 1 (HO-1) and ferritin besides sequestosome (SQSMT1 or p62)
 were found in the NRF2 CPs and the NRF2 UTFs. Differences in the
 involvement of iron metabolism pathway in Leishmania infection was
 revealed by the presence of HO-1 and ferritin. Noteworty, HO-1 was
 strongly associated with L. amazonensis infection, while ferritin was
 regulated by both species. As expected, higher HO-1 and p62 expressions
 were validated in L. amazonensis-infected BMMØ, in addition to decreased
 expression of ferritin and nitric oxide production. Moreover, BMMØ
 incubated with L. amazonensis LPG also expressed higher levels of HO-1 in
 comparison to those stimulated with L. major LPG. In addition, L.
 amazonensis-induced uptake of holoTf was higher than that induced by L.
 major in BMMØ, and holoTf was also detected at higher levels in vacuoles
 induced by L. amazonensis. Taken together, these findings indicate that
 NRF2 pathway activation and increased HO-1 production, together with
 higher levels of holoTf uptake, may promote permissiveness to L.
 amazonensis infection. In this context, differences in protein signatures
 triggered in the host by L. amazonensis and L. major infection could drive
 the outcomes in distinct clinical forms of leishmaniasis.
description: Proteomic analysis of
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