DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination
BackgroundLeishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful Leishmania infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophil...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.750648/full |
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| author | Rafael Tiburcio Rafael Tiburcio Léon Dimitri Melo Léon Dimitri Melo Sara Nunes Sara Nunes Ana Luísa Augusto Barbosa Elaine Carvalho de Oliveira Elaine Carvalho de Oliveira Martha Suarez Martha Suarez Valéria M. Borges Valéria M. Borges Natalia Tavares Natalia Tavares Claudia Ida Brodskyn Claudia Ida Brodskyn Claudia Ida Brodskyn |
| author_facet | Rafael Tiburcio Rafael Tiburcio Léon Dimitri Melo Léon Dimitri Melo Sara Nunes Sara Nunes Ana Luísa Augusto Barbosa Elaine Carvalho de Oliveira Elaine Carvalho de Oliveira Martha Suarez Martha Suarez Valéria M. Borges Valéria M. Borges Natalia Tavares Natalia Tavares Claudia Ida Brodskyn Claudia Ida Brodskyn Claudia Ida Brodskyn |
| author_sort | Rafael Tiburcio |
| collection | DOAJ |
| description | BackgroundLeishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful Leishmania infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophils (PMNs) and dendritic cells (DCs) in the establishment of immunological responses against these parasites. However, few studies, contemplate to what extent these cells interact synergistically to constrain Leishmania infection.ObjectiveWe sought to investigate how PMNs and infected DCs interact in an in vitro model of Leishmania amazonensis infection.Material and MethodsBriefly, human PMNs and DCs were purified from the peripheral blood of healthy donors. Next, PMNs were activated with fibronectin and subsequently co-cultured with L. amazonensis-infected DCs.ResultsWe observed that L. amazonensis-infected DC exhibited lower rates of infection when co-cultivated with either resting or activated PMNs. Surprisingly, we found that the release of neutrophil enzymes was not involved in Leishmania killing. Next, we showed that the interaction between PMNs and infected-DCs was intermediated by DC-SIGN, further suggesting that parasite elimination occurs in a contact-dependent manner. Furthermore, we also observed that TNFα and ROS production was dependent on DC-SIGN-mediated contact, as well as parasite elimination is dependent on TNFα production in the co-culture. Finally, we observed that direct contact between PMNs and DCs are required to restore the expression of DC maturation molecules during L. amazonensis infection.ConclusionOur findings suggest that the engagement of direct contact between PMNs and L. amazonensis-infected DC via DC-SIGN is required for the production of inflammatory mediators with subsequent parasite elimination and DC maturation. |
| first_indexed | 2024-12-20T23:31:53Z |
| format | Article |
| id | doaj.art-a1c509ee2a4443058889d70b3654156c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T23:31:53Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a1c509ee2a4443058889d70b3654156c2022-12-21T19:23:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.750648750648DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite EliminationRafael Tiburcio0Rafael Tiburcio1Léon Dimitri Melo2Léon Dimitri Melo3Sara Nunes4Sara Nunes5Ana Luísa Augusto Barbosa6Elaine Carvalho de Oliveira7Elaine Carvalho de Oliveira8Martha Suarez9Martha Suarez10Valéria M. Borges11Valéria M. Borges12Natalia Tavares13Natalia Tavares14Claudia Ida Brodskyn15Claudia Ida Brodskyn16Claudia Ida Brodskyn17Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilInstituto de Investigação em Imunologia - Instituto de nacional de ciência e tecnologia (iii-INCT), São Paulo, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BrazilInstituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BrazilInstituto de Investigação em Imunologia - Instituto de nacional de ciência e tecnologia (iii-INCT), São Paulo, BrazilBackgroundLeishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful Leishmania infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophils (PMNs) and dendritic cells (DCs) in the establishment of immunological responses against these parasites. However, few studies, contemplate to what extent these cells interact synergistically to constrain Leishmania infection.ObjectiveWe sought to investigate how PMNs and infected DCs interact in an in vitro model of Leishmania amazonensis infection.Material and MethodsBriefly, human PMNs and DCs were purified from the peripheral blood of healthy donors. Next, PMNs were activated with fibronectin and subsequently co-cultured with L. amazonensis-infected DCs.ResultsWe observed that L. amazonensis-infected DC exhibited lower rates of infection when co-cultivated with either resting or activated PMNs. Surprisingly, we found that the release of neutrophil enzymes was not involved in Leishmania killing. Next, we showed that the interaction between PMNs and infected-DCs was intermediated by DC-SIGN, further suggesting that parasite elimination occurs in a contact-dependent manner. Furthermore, we also observed that TNFα and ROS production was dependent on DC-SIGN-mediated contact, as well as parasite elimination is dependent on TNFα production in the co-culture. Finally, we observed that direct contact between PMNs and DCs are required to restore the expression of DC maturation molecules during L. amazonensis infection.ConclusionOur findings suggest that the engagement of direct contact between PMNs and L. amazonensis-infected DC via DC-SIGN is required for the production of inflammatory mediators with subsequent parasite elimination and DC maturation.https://www.frontiersin.org/articles/10.3389/fimmu.2021.750648/fullleishmaniasispolymorphonuclear cellsmonocyte-derived dendritic cellsDC-SIGNDC maturation markers |
| spellingShingle | Rafael Tiburcio Rafael Tiburcio Léon Dimitri Melo Léon Dimitri Melo Sara Nunes Sara Nunes Ana Luísa Augusto Barbosa Elaine Carvalho de Oliveira Elaine Carvalho de Oliveira Martha Suarez Martha Suarez Valéria M. Borges Valéria M. Borges Natalia Tavares Natalia Tavares Claudia Ida Brodskyn Claudia Ida Brodskyn Claudia Ida Brodskyn DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination Frontiers in Immunology leishmaniasis polymorphonuclear cells monocyte-derived dendritic cells DC-SIGN DC maturation markers |
| title | DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination |
| title_full | DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination |
| title_fullStr | DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination |
| title_full_unstemmed | DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination |
| title_short | DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination |
| title_sort | dc sign mediates the interaction between neutrophils and leishmania amazonensis infected dendritic cells to promote dc maturation and parasite elimination |
| topic | leishmaniasis polymorphonuclear cells monocyte-derived dendritic cells DC-SIGN DC maturation markers |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.750648/full |
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