Proteomic Analysis Reveals a Predominant NFE2L2 (NRF2) Signature in Canonical Pathway and Upstream Regulator Analysis of Leishmania-Infected Macrophages

dc.creatorMenezes, Juliana Perrone Bezerra de
dc.creatorCunha, Antonio Ricardo Khouri
dc.creatorOliveira, Camila Victoria Sousa
dc.creatorPetersen, Antonio Luis de Oliveira Almeida
dc.creatorAlmeida, Tais Fontoura de
dc.creatorMendes, Flávia R. L.
dc.creatorRebouças, Amanda do Amor Divino
dc.creatorLorentz, Amanda Lopes
dc.creatorLuz, Nívea Farias
dc.creatorLima, Jonilson Berlink
dc.creatorRamos, Pablo Ivan Pereira
dc.creatorSoares, Rodrigo Pedro
dc.creatorRugani, Jeronimo Nunes
dc.creatorBuck, Gregory A.
dc.creatorKrieger, Marco Aurélio
dc.creatorMarchini, Fabrício Klerynton
dc.creatorVivarini, Áislan de Carvalho
dc.creatorLopes, Ulisses Gazos
dc.creatorBorges, Valéria de Matos
dc.creatorVeras, Patrícia Sampaio Tavares
dc.date2019-07-16T12:33:35Z
dc.date2019-07-16T12:33:35Z
dc.date2019
dc.date.accessioned2023-09-27T00:11:07Z
dc.date.available2023-09-27T00:11:07Z
dc.identifierMENEZES, Juliana Perrone Bezerra de et al. Proteomic Analysis Reveals a Predominant NFE2L2 (NRF2) Signature in Canonical Pathway and Upstream Regulator Analysis of Leishmania-Infected Macrophages. Frontiers in Immunology, p. 1-17, June 2019.
dc.identifier1664-3224
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/34131
dc.identifier10.3389/fimmu.2019.01362
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898295
dc.descriptionFundação de Amparo à Pesquisa do Estado da Bahia (PV http://www.fapesb.ba.gov.br), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br) and National Institute of Science and Technology of Tropical Disease (PV http://inct.cnpq.br/ web/inct-dt). VB, PV, and UL are senior investigators funded by CNPq.
dc.descriptionCBA 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectLeishmania
dc.subjectMacrófagos
dc.subjectNRF2
dc.subjectCamundongos CBA
dc.subjectMetabolismo do ferro
dc.subjectLeishmania
dc.subjectMacrophage
dc.subjectNRF2
dc.subjectCBA mice
dc.subjectIron metabolism
dc.titleProteomic Analysis Reveals a Predominant NFE2L2 (NRF2) Signature in Canonical Pathway and Upstream Regulator Analysis of Leishmania-Infected Macrophages
dc.typeArticle


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