| Author | Luz, Nivea Farias | |
| Author | Balaji, Sakthi | |
| Author | Okuda, Kendi | |
| Author | Barreto, Aline Silva | |
| Author | Bertin, John | |
| Author | Gough, Peter J | |
| Author | Gazzinelli, Ricardo Tostes | |
| Author | Almeida, Roque Pacheco de | |
| Author | Bozza, Marcelo Torres | |
| Author | Borges, Valeria de Matos | |
| Author | Chan, Francis Ka-Ming | |
| Access date | 2017-05-16T17:24:36Z | |
| Available date | 2017-05-16T17:24:36Z | |
| Document date | 2016 | |
| Citation | LUZ, N. F. et al. RIPK1 and PGAM5 Control Leishmania Replication through Distinct Mechanisms. The Journal of Immunology, v. 196, 2016. | pt_BR |
| ISSN | 0022-1767 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/18872 | |
| Sponsorship | National Institutes of Health Grant AI119030 (to F.K.-M.C.), the Fundação de Amparo à Pesquisa do Estado da Bahia (to V.M.B.), and a postdoctoral fellowship from Conselho Nacional de Desenvolvimento Científico e
Tecnológico (to N.F.L.). | pt_BR |
| Language | eng | pt_BR |
| Publisher | American Association of Immunologists, Inc. | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Leishmania | pt_BR |
| Subject in Portuguese | Leishmaniose Cutânea | pt_BR |
| Subject in Portuguese | Morte celular | pt_BR |
| Subject in Portuguese | Proteína quinase | pt_BR |
| Subject in Portuguese | Heme | pt_BR |
| Subject in Portuguese | Medula óssea | pt_BR |
| Subject in Portuguese | Macrófagos | pt_BR |
| Title | RIPK1 and PGAM5 Control Leishmania Replication through Distinct Mechanisms | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.4049/jimmunol.1502492 | |
| Abstract | Leishmaniasis is an important parasitic disease found in the tropics and subtropics. Cutaneous and visceral leishmaniasis affect an estimated 1.5 million people worldwide. Despite its human health relevance, relatively little is known about the cell death pathways that control Leishmania replication in the host. Necroptosis is a recently identified form of cell death with potent antiviral effects. Receptor interacting protein kinase 1 (RIPK1) is a critical kinase that mediates necroptosis downstream of death receptors and TLRs. Heme, a product of hemoglobin catabolism during certain intracellular pathogen infections, is also a potent inducer of macrophage necroptosis. We found that human visceral leishmaniasis patients exhibit elevated serum levels of heme. Therefore, we examined the impact of heme and necroptosis on Leishmania replication. Indeed, heme potently inhibited Leishmania replication in bone marrow-derived macrophages. Moreover, we found that inhibition of RIPK1 kinase activity also enhanced parasite replication in the absence of heme. We further found that the mitochondrial phosphatase phosphoglycerate mutase family member 5 (PGAM5), a putative downstream effector of RIPK1, was also required for inhibition of Leishmania replication. In mouse infection, both PGAM5 and RIPK1 kinase activity are required for IL-1β expression in response to Leishmania However, PGAM5, but not RIPK1 kinase activity, was directly responsible for Leishmania-induced IL-1β secretion and NO production in bone marrow-derived macrophages. Collectively, these results revealed that RIPK1 and PGAM5 function independently to exert optimal control of Leishmania replication in the host. | pt_BR |
| Affilliation | University of Massachusetts Medical School. Department of Pathology. Worcester, MA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | University of Massachusetts Medical School. Department of Pathology. Worcester, MA | pt_BR |
| Affilliation | University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Departamento de Medicina. Aracaju, SE, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratorio de Imunopatologia. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Pattern Recognition Receptor Discovery Performance Unit. Immuno-Inflammation Therapeutic Area, GlaxoSmithKline. Collegeville, PA | pt_BR |
| Affilliation | University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA / Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratorio de Imunopatologia. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Sergipe. Hospital Universitário. Departamento de Medicina. Aracaju, SE, Brasil | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunologia, Rio de Janeiro, RJ, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | University of Massachusetts Medical School. Immunology and Microbiology Program. Worcester, MA / University of Massachusetts Medical School. Department of Pathology. Worcester, MA | pt_BR |
| Subject | Leishmania | pt_BR |
| Subject | Leishmaniasis, Cutaneous | pt_BR |
| Subject | Cell death | pt_BR |
| Subject | Protein kinase | pt_BR |
| Subject | Heme | pt_BR |
| Subject | Bone marrow | pt_BR |
| Subject | Macrophages | pt_BR |
| DeCS | Leishmania | pt_BR |
| DeCS | Leishmaniose Cutanea | pt_BR |
| DeCS | Morte celular | pt_BR |
| DeCS | Kinase | pt_BR |
| DeCS | Medula óssea | pt_BR |
| DeCS | Heme | pt_BR |
| DeCS | Macrófagos | pt_BR |
