Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo
Cutaneous leishmaniasis, caused by Leishmania braziliensis, still represents a serious health problem in Brazil, especially in the northeast region. Currently, to our knowledge, no report describes the role of hypoxia inducible factor-1α (HIF-1α) during L braziliensis infection. In this study, we de...
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Elsevier
2025-05-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000013 |
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| author | Rodrigo C.O. Sanches Leonardo G. Vaz Fabio V. Marinho Erika S. Guimarães Edgar M. Carvalho Lucas P. Carvalho Sergio C. Oliveira |
| author_facet | Rodrigo C.O. Sanches Leonardo G. Vaz Fabio V. Marinho Erika S. Guimarães Edgar M. Carvalho Lucas P. Carvalho Sergio C. Oliveira |
| author_sort | Rodrigo C.O. Sanches |
| collection | DOAJ |
| description | Cutaneous leishmaniasis, caused by Leishmania braziliensis, still represents a serious health problem in Brazil, especially in the northeast region. Currently, to our knowledge, no report describes the role of hypoxia inducible factor-1α (HIF-1α) during L braziliensis infection. In this study, we demonstrated that the parasite induces HIF-1α expression and stabilization in bone marrow–derived macrophages only when added with exogenous IFN-γ plus lipopolysaccharide. Coherently, we did not find an enrichment in the glycolytic pathway upon bone marrow–derived macrophage infection. Evaluating the impact of HIF-1α absence during macrophage infection in vitro, we observed HIF-1α–knockout cells present at high levels of IL-10, reduced production of nitric oxide, and decreased expression of VEGF-A. As a result, parasite viability improves within HIF-1α–knockout cells. However, in vivo, the absence of myeloid cells expressing HIF-1α had no influence on nitric oxide at tissue levels and in parasite burden. Conversely, lack of HIF-1α significantly affects L braziliensis–induced pathology. Ear lesions induced in myeloid HIF-1α–knockout mice were thicker, presenting higher frequency of macrophages, neutrophils, CD4+, and CD8+ T cells as well as higher levels of IL-12, IL-1β, and IFN-γ, compared with those in wild-type mice. Moreover, draining lymph nodes from myeloid HIF-1α–knockout mice also harbored increased populations of T cells. Our data demonstrate that HIF-1α plays an important role during L braziliensis infection influencing skin pathology in vivo. |
| format | Article |
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| institution | Kabale University |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-5bfcd7e8eb5d4079afe921f7b267637f2025-02-06T05:12:59ZengElsevierJID Innovations2667-02672025-05-0153100347Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In VivoRodrigo C.O. Sanches0Leonardo G. Vaz1Fabio V. Marinho2Erika S. Guimarães3Edgar M. Carvalho4Lucas P. Carvalho5Sergio C. Oliveira6Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilServiço de Imunologia, Complexo Hospitalar Professor Edgar Santos, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Pesquisas Clínicas (LAPEC), Instituto Gonçalo Moniz (IGM), Fiocruz, Salvador, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, BrazilServiço de Imunologia, Complexo Hospitalar Professor Edgar Santos, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Pesquisas Clínicas (LAPEC), Instituto Gonçalo Moniz (IGM), Fiocruz, Salvador, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, Brazil; Institut Pasteur de São Paulo, São Paulo, Brazil; Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; Correspondence: Sergio C. Oliveira, Departamento de Imunologia, Universidade de São Paulo, Ave Prof Lineu Prestes, 1730São Paulo, São Paulo 05508-000, Brazil.Cutaneous leishmaniasis, caused by Leishmania braziliensis, still represents a serious health problem in Brazil, especially in the northeast region. Currently, to our knowledge, no report describes the role of hypoxia inducible factor-1α (HIF-1α) during L braziliensis infection. In this study, we demonstrated that the parasite induces HIF-1α expression and stabilization in bone marrow–derived macrophages only when added with exogenous IFN-γ plus lipopolysaccharide. Coherently, we did not find an enrichment in the glycolytic pathway upon bone marrow–derived macrophage infection. Evaluating the impact of HIF-1α absence during macrophage infection in vitro, we observed HIF-1α–knockout cells present at high levels of IL-10, reduced production of nitric oxide, and decreased expression of VEGF-A. As a result, parasite viability improves within HIF-1α–knockout cells. However, in vivo, the absence of myeloid cells expressing HIF-1α had no influence on nitric oxide at tissue levels and in parasite burden. Conversely, lack of HIF-1α significantly affects L braziliensis–induced pathology. Ear lesions induced in myeloid HIF-1α–knockout mice were thicker, presenting higher frequency of macrophages, neutrophils, CD4+, and CD8+ T cells as well as higher levels of IL-12, IL-1β, and IFN-γ, compared with those in wild-type mice. Moreover, draining lymph nodes from myeloid HIF-1α–knockout mice also harbored increased populations of T cells. Our data demonstrate that HIF-1α plays an important role during L braziliensis infection influencing skin pathology in vivo.http://www.sciencedirect.com/science/article/pii/S2667026725000013HIF-1αImmunometabolismInnate immunityLeishmania braziliensisSkin pathology |
| spellingShingle | Rodrigo C.O. Sanches Leonardo G. Vaz Fabio V. Marinho Erika S. Guimarães Edgar M. Carvalho Lucas P. Carvalho Sergio C. Oliveira Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo JID Innovations HIF-1α Immunometabolism Innate immunity Leishmania braziliensis Skin pathology |
| title | Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo |
| title_full | Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo |
| title_fullStr | Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo |
| title_full_unstemmed | Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo |
| title_short | Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo |
| title_sort | lack of hypoxia inducible factor 1α influences on macrophages ability to deal with leishmania braziliensis in vitro and affects pathology in vivo |
| topic | HIF-1α Immunometabolism Innate immunity Leishmania braziliensis Skin pathology |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000013 |
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