Data from: Proteomic analysis reveals a predominant NFE2L2 (NRF2) signature in the ​canonical pathway and upstream regulator analysis of Leishmania-infected macrophages

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.