Publicação
CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease
| Resumo: | Aspergillus fumigatus is a model fungal pathogen and a common cause of infection in individuals with the primary immunodeficiency chronic granulomatous disease (CGD). Although primarily considered a deficiency of innate immunity, CGD is also linked to dysfunctional T cell reactivity. Both CD4+ and CD8+ T cells mediate vaccine-induced protection from experimental aspergillosis, but the molecular mechanisms leading to the generation of protective immunity and whether these mechanisms are dysregulated in individuals with CGD have not been determined. Here, we show that activation of either T cell subset in a mouse model of CGD is contingent upon the nature of the fungal vaccine, the involvement of distinct innate receptor signaling pathways, and the mode of antigen routing and presentation in DCs. Aspergillus conidia activated CD8+ T cells upon sorting to the Rab14+ endosomal compartment required for alternative MHC class I presentation. Cross-priming of CD8+ T cells failed to occur in mice with CGD due to defective DC endosomal alkalinization and autophagy. However, long-lasting antifungal protection and disease control were successfully achieved upon vaccination with purified fungal antigens that activated CD4+ T cells through the endosome/lysosome pathway. Our study thus indicates that distinct intracellular pathways are exploited for the priming of CD4+ and CD8+ T cells to A. fumigatus and suggests that CD4+ T cell vaccination may be able to overcome defective antifungal CD8+ T cell memory in individuals with CGD. |
|---|---|
| Autores principais: | Luca, Antonella De |
| Outros Autores: | Iannitti, Rossana G.; Bozza, Silvia; Beau, Remi; Casagrande, Andrea; D’Angelo, Carmen; Moretti, Silvia; Cunha, Cristina; Giovannini, Gloria; Massi-Benedetti, Cristina; Carvalho, Agostinho; Boon, Louis; Latgé, Jean-Paul; Romani, Luigina |
| Ano: | 2012 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867439309621035008 |
|---|---|
| author | Luca, Antonella De |
| author2 | Iannitti, Rossana G. Bozza, Silvia Beau, Remi Casagrande, Andrea D’Angelo, Carmen Moretti, Silvia Cunha, Cristina Giovannini, Gloria Massi-Benedetti, Cristina Carvalho, Agostinho Boon, Louis Latgé, Jean-Paul Romani, Luigina |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Luca, Antonella De Iannitti, Rossana G. Bozza, Silvia Beau, Remi Casagrande, Andrea D’Angelo, Carmen Moretti, Silvia Cunha, Cristina Giovannini, Gloria Massi-Benedetti, Cristina Carvalho, Agostinho Boon, Louis Latgé, Jean-Paul Romani, Luigina |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Luca, Antonella De\"},{\"Person.name\":\"Iannitti, Rossana G.\"},{\"Person.name\":\"Bozza, Silvia\"},{\"Person.name\":\"Beau, Remi\"},{\"Person.name\":\"Casagrande, Andrea\"},{\"Person.name\":\"D’Angelo, Carmen\"},{\"Person.name\":\"Moretti, Silvia\"},{\"Person.name\":\"Cunha, Cristina\"},{\"Person.name\":\"Giovannini, Gloria\"},{\"Person.name\":\"Massi-Benedetti, Cristina\"},{\"Person.name\":\"Carvalho, Agostinho\"},{\"Person.name\":\"Boon, Louis\"},{\"Person.name\":\"Latgé, Jean-Paul\"},{\"Person.name\":\"Romani, Luigina\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Luca, Antonella De Iannitti, Rossana G. Bozza, Silvia Beau, Remi Casagrande, Andrea D’Angelo, Carmen Moretti, Silvia Cunha, Cristina Giovannini, Gloria Massi-Benedetti, Cristina Carvalho, Agostinho Boon, Louis Latgé, Jean-Paul Romani, Luigina |
| datacite.date.Accepted.fl_str_mv | 2012-05-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2013-05-03T11:21:46Z |
| datacite.date.embargoed.fl_str_mv | 2013-05-03T11:21:46Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.titles.title.fl_str_mv | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Luca, Antonella De Iannitti, Rossana G. Bozza, Silvia Beau, Remi Casagrande, Andrea D’Angelo, Carmen Moretti, Silvia Cunha, Cristina Giovannini, Gloria Massi-Benedetti, Cristina Carvalho, Agostinho Boon, Louis Latgé, Jean-Paul Romani, Luigina |
| dc.date.Accepted.fl_str_mv | 2012-05-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2013-05-03T11:21:46Z |
| dc.date.embargoed.fl_str_mv | 2013-05-03T11:21:46Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/23919 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | American Society for Clinical Investigation |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.title.fl_str_mv | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Aspergillus fumigatus is a model fungal pathogen and a common cause of infection in individuals with the primary immunodeficiency chronic granulomatous disease (CGD). Although primarily considered a deficiency of innate immunity, CGD is also linked to dysfunctional T cell reactivity. Both CD4+ and CD8+ T cells mediate vaccine-induced protection from experimental aspergillosis, but the molecular mechanisms leading to the generation of protective immunity and whether these mechanisms are dysregulated in individuals with CGD have not been determined. Here, we show that activation of either T cell subset in a mouse model of CGD is contingent upon the nature of the fungal vaccine, the involvement of distinct innate receptor signaling pathways, and the mode of antigen routing and presentation in DCs. Aspergillus conidia activated CD8+ T cells upon sorting to the Rab14+ endosomal compartment required for alternative MHC class I presentation. Cross-priming of CD8+ T cells failed to occur in mice with CGD due to defective DC endosomal alkalinization and autophagy. However, long-lasting antifungal protection and disease control were successfully achieved upon vaccination with purified fungal antigens that activated CD4+ T cells through the endosome/lysosome pathway. Our study thus indicates that distinct intracellular pathways are exploited for the priming of CD4+ and CD8+ T cells to A. fumigatus and suggests that CD4+ T cell vaccination may be able to overcome defective antifungal CD8+ T cell memory in individuals with CGD. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/1bffc6da-6bf1-4fe6-9844-30d5cab96f32/download |
| id | rum_4c8bcb984e2c74ea64b331b6bc538227 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/23919 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/23919 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Luca, Antonella De Iannitti, Rossana G. Bozza, Silvia Beau, Remi Casagrande, Andrea D’Angelo, Carmen Moretti, Silvia Cunha, Cristina Giovannini, Gloria Massi-Benedetti, Cristina Carvalho, Agostinho Boon, Louis Latgé, Jean-Paul Romani, Luigina |
| publishDate | 2012 |
| publisher.none.fl_str_mv | American Society for Clinical Investigation |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engAmerican Society for Clinical InvestigationporAspergillus fumigatus is a model fungal pathogen and a common cause of infection in individuals with the primary immunodeficiency chronic granulomatous disease (CGD). Although primarily considered a deficiency of innate immunity, CGD is also linked to dysfunctional T cell reactivity. Both CD4+ and CD8+ T cells mediate vaccine-induced protection from experimental aspergillosis, but the molecular mechanisms leading to the generation of protective immunity and whether these mechanisms are dysregulated in individuals with CGD have not been determined. Here, we show that activation of either T cell subset in a mouse model of CGD is contingent upon the nature of the fungal vaccine, the involvement of distinct innate receptor signaling pathways, and the mode of antigen routing and presentation in DCs. Aspergillus conidia activated CD8+ T cells upon sorting to the Rab14+ endosomal compartment required for alternative MHC class I presentation. Cross-priming of CD8+ T cells failed to occur in mice with CGD due to defective DC endosomal alkalinization and autophagy. However, long-lasting antifungal protection and disease control were successfully achieved upon vaccination with purified fungal antigens that activated CD4+ T cells through the endosome/lysosome pathway. Our study thus indicates that distinct intracellular pathways are exploited for the priming of CD4+ and CD8+ T cells to A. fumigatus and suggests that CD4+ T cell vaccination may be able to overcome defective antifungal CD8+ T cell memory in individuals with CGD.application/pdfporCD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous diseaseLuca, Antonella DeIannitti, Rossana G.Bozza, SilviaBeau, RemiCasagrande, AndreaD’Angelo, CarmenMoretti, SilviaCunha, CristinaGiovannini, GloriaMassi-Benedetti, CristinaCarvalho, AgostinhoBoon, LouisLatgé, Jean-PaulRomani, LuiginaHostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptPMID22523066ISSNIsPartOf0021-9738DOIIsPartOf10.1172/JCI608622013-05-03T11:21:46Z2012-052012-05-01T00:00:00ZHandlehttps://hdl.handle.net/1822/23919http://purl.org/coar/access_right/c_abf2open access5940842 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/1bffc6da-6bf1-4fe6-9844-30d5cab96f32/download |
| spellingShingle | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease Luca, Antonella De |
| status | SINGLETON |
| title | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| title_full | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| title_fullStr | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| title_full_unstemmed | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| title_short | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| title_sort | CD4+ T cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease |
| url | https://hdl.handle.net/1822/23919 |
| visible | 1 |