Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils
Visceral leishmaniasis (VL) is often associated with hematologic manifestations that may interfere with neutrophil response. Lipophosphoglycan (LPG) is a major molecule on the surface of Leishmania promastigotes, which has been associated with several aspects of the parasite–vector–host interplay. H...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.788196/full |
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| author | Graziele Quintela-Carvalho Graziele Quintela-Carvalho Graziele Quintela-Carvalho Astrid Madeleine Calero Goicochea Astrid Madeleine Calero Goicochea Vanessa Mançur-Santos Vanessa Mançur-Santos Sayonara de Melo Viana Sayonara de Melo Viana Yasmin da Silva Luz Yasmin da Silva Luz Beatriz Rocha Simões Dias Beatriz Rocha Simões Dias Milena Lázaro-Souza Milena Lázaro-Souza Martha Suarez Martha Suarez Camila Indiani de Oliveira Camila Indiani de Oliveira Elvira M. Saraiva Cláudia I. Brodskyn Cláudia I. Brodskyn Patrícia T. Veras Patrícia T. Veras Juliana P.B. de Menezes Juliana P.B. de Menezes Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Jonilson Berlink Lima Albert Descoteaux Valéria M. Borges Valéria M. Borges |
| author_facet | Graziele Quintela-Carvalho Graziele Quintela-Carvalho Graziele Quintela-Carvalho Astrid Madeleine Calero Goicochea Astrid Madeleine Calero Goicochea Vanessa Mançur-Santos Vanessa Mançur-Santos Sayonara de Melo Viana Sayonara de Melo Viana Yasmin da Silva Luz Yasmin da Silva Luz Beatriz Rocha Simões Dias Beatriz Rocha Simões Dias Milena Lázaro-Souza Milena Lázaro-Souza Martha Suarez Martha Suarez Camila Indiani de Oliveira Camila Indiani de Oliveira Elvira M. Saraiva Cláudia I. Brodskyn Cláudia I. Brodskyn Patrícia T. Veras Patrícia T. Veras Juliana P.B. de Menezes Juliana P.B. de Menezes Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Jonilson Berlink Lima Albert Descoteaux Valéria M. Borges Valéria M. Borges |
| author_sort | Graziele Quintela-Carvalho |
| collection | DOAJ |
| description | Visceral leishmaniasis (VL) is often associated with hematologic manifestations that may interfere with neutrophil response. Lipophosphoglycan (LPG) is a major molecule on the surface of Leishmania promastigotes, which has been associated with several aspects of the parasite–vector–host interplay. Here, we investigated how LPG from Leishmania (L.) infantum, the principal etiological agent of VL in the New World, influences the initial establishment of infection during interaction with human neutrophils in an experimental setting in vitro. Human neutrophils obtained from peripheral blood samples were infected with either the wild-type L. infantum (WT) strain or LPG-deficient mutant (∆lpg1). In this setting, ∆lpg1 parasites displayed reduced viability compared to WT L. infantum; such finding was reverted in the complemented ∆lpg1+LPG1 parasites at 3- and 6-h post-infection. Confocal microscopy experiments indicated that this decreased survival was related to enhanced lysosomal fusion. In fact, LPG-deficient L. infantum parasites more frequently died inside neutrophil acidic compartments, a phenomenon that was reverted when host cells were treated with Wortmannin. We also observed an increase in the secretion of the neutrophil collagenase matrix metalloproteinase-8 (MMP-8) by cells infected with ∆lpg1 L. infantum compared to those that were infected with WT parasites. Furthermore, collagen I matrix degradation was found to be significantly increased in ∆lpg1 parasite-infected cells but not in WT-infected controls. Flow cytometry analysis revealed a substantial boost in production of reactive oxygen species (ROS) during infection with either WT or ∆lpg1 L. infantum. In addition, killing of ∆lpg1 parasites was shown to be more dependent on the ROS production than that of WT L. infantum. Notably, inhibition of the oxidative stress with Apocynin potentially fueled ∆lpg1 L. infantum fitness as it increased the intracellular parasite viability. Thus, our observations demonstrate that LPG may be a critical molecule fostering parasite survival in human neutrophils through a mechanism that involves cellular activation and generation of free radicals. |
| first_indexed | 2024-12-21T11:01:33Z |
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| id | doaj.art-e1874953b74a4c91bd800bf9bfd8eb75 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-21T11:01:33Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-e1874953b74a4c91bd800bf9bfd8eb752022-12-21T19:06:21ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-04-011210.3389/fcimb.2022.788196788196Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human NeutrophilsGraziele Quintela-Carvalho0Graziele Quintela-Carvalho1Graziele Quintela-Carvalho2Astrid Madeleine Calero Goicochea3Astrid Madeleine Calero Goicochea4Vanessa Mançur-Santos5Vanessa Mançur-Santos6Sayonara de Melo Viana7Sayonara de Melo Viana8Yasmin da Silva Luz9Yasmin da Silva Luz10Beatriz Rocha Simões Dias11Beatriz Rocha Simões Dias12Milena Lázaro-Souza13Milena Lázaro-Souza14Martha Suarez15Martha Suarez16Camila Indiani de Oliveira17Camila Indiani de Oliveira18Elvira M. Saraiva19Cláudia I. Brodskyn20Cláudia I. Brodskyn21Patrícia T. Veras22Patrícia T. Veras23Juliana P.B. de Menezes24Juliana P.B. de Menezes25Bruno B. Andrade26Bruno B. Andrade27Bruno B. Andrade28Bruno B. Andrade29Bruno B. Andrade30Bruno B. Andrade31Jonilson Berlink Lima32Albert Descoteaux33Valéria M. Borges34Valéria M. Borges35Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Federal de Educação, Ciência e Tecnologia Baiano (IFBaiano), Alagoinhas, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilDepartamento de Imunologia, Laboratório de Imunobiologia das Leishmanioses, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilEscola Bahiana de Medicina e Saúde Pública, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilCurso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, BrazilUniversidade Salvador (UNIFACS), Laureate Universities, Salvador, BrazilNúcleo de Agentes Infecciosos e Vetores (NAIVE), Universidade Federal do Oeste da Bahia (UFOB), Barreiras, Brazil0Institut National de la Recherche Scientifique (INRS)–Centre Armand-Frappier Santé Biotechnologie, Laval, QC, CanadaInstituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia (UFBA), Salvador, BrazilVisceral leishmaniasis (VL) is often associated with hematologic manifestations that may interfere with neutrophil response. Lipophosphoglycan (LPG) is a major molecule on the surface of Leishmania promastigotes, which has been associated with several aspects of the parasite–vector–host interplay. Here, we investigated how LPG from Leishmania (L.) infantum, the principal etiological agent of VL in the New World, influences the initial establishment of infection during interaction with human neutrophils in an experimental setting in vitro. Human neutrophils obtained from peripheral blood samples were infected with either the wild-type L. infantum (WT) strain or LPG-deficient mutant (∆lpg1). In this setting, ∆lpg1 parasites displayed reduced viability compared to WT L. infantum; such finding was reverted in the complemented ∆lpg1+LPG1 parasites at 3- and 6-h post-infection. Confocal microscopy experiments indicated that this decreased survival was related to enhanced lysosomal fusion. In fact, LPG-deficient L. infantum parasites more frequently died inside neutrophil acidic compartments, a phenomenon that was reverted when host cells were treated with Wortmannin. We also observed an increase in the secretion of the neutrophil collagenase matrix metalloproteinase-8 (MMP-8) by cells infected with ∆lpg1 L. infantum compared to those that were infected with WT parasites. Furthermore, collagen I matrix degradation was found to be significantly increased in ∆lpg1 parasite-infected cells but not in WT-infected controls. Flow cytometry analysis revealed a substantial boost in production of reactive oxygen species (ROS) during infection with either WT or ∆lpg1 L. infantum. In addition, killing of ∆lpg1 parasites was shown to be more dependent on the ROS production than that of WT L. infantum. Notably, inhibition of the oxidative stress with Apocynin potentially fueled ∆lpg1 L. infantum fitness as it increased the intracellular parasite viability. Thus, our observations demonstrate that LPG may be a critical molecule fostering parasite survival in human neutrophils through a mechanism that involves cellular activation and generation of free radicals.https://www.frontiersin.org/articles/10.3389/fcimb.2022.788196/fulllipophosphoglycanLeishmania infantumneutrophilsROSinfection |
| spellingShingle | Graziele Quintela-Carvalho Graziele Quintela-Carvalho Graziele Quintela-Carvalho Astrid Madeleine Calero Goicochea Astrid Madeleine Calero Goicochea Vanessa Mançur-Santos Vanessa Mançur-Santos Sayonara de Melo Viana Sayonara de Melo Viana Yasmin da Silva Luz Yasmin da Silva Luz Beatriz Rocha Simões Dias Beatriz Rocha Simões Dias Milena Lázaro-Souza Milena Lázaro-Souza Martha Suarez Martha Suarez Camila Indiani de Oliveira Camila Indiani de Oliveira Elvira M. Saraiva Cláudia I. Brodskyn Cláudia I. Brodskyn Patrícia T. Veras Patrícia T. Veras Juliana P.B. de Menezes Juliana P.B. de Menezes Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Jonilson Berlink Lima Albert Descoteaux Valéria M. Borges Valéria M. Borges Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils Frontiers in Cellular and Infection Microbiology lipophosphoglycan Leishmania infantum neutrophils ROS infection |
| title | Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils |
| title_full | Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils |
| title_fullStr | Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils |
| title_full_unstemmed | Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils |
| title_short | Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils |
| title_sort | leishmania infantum defective in lipophosphoglycan biosynthesis interferes with activation of human neutrophils |
| topic | lipophosphoglycan Leishmania infantum neutrophils ROS infection |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.788196/full |
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