Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses
Abstract Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that pr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54644-w |
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| author | Irshad Ahmed Hajam Chih-Ming Tsai Cesia Gonzalez Juan Raphael Caldera María Lázaro Díez Xin Du April Aralar Brian Lin William Duong George Y. Liu |
| author_facet | Irshad Ahmed Hajam Chih-Ming Tsai Cesia Gonzalez Juan Raphael Caldera María Lázaro Díez Xin Du April Aralar Brian Lin William Duong George Y. Liu |
| author_sort | Irshad Ahmed Hajam |
| collection | DOAJ |
| description | Abstract Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4+ T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4+ T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4+ T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4+ T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development. |
| format | Article |
| id | doaj-art-bef39520896347868e6bc6b1b802bac6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bef39520896347868e6bc6b1b802bac62024-12-22T12:35:54ZengNature PortfolioNature Communications2041-17232024-12-0115111610.1038/s41467-024-54644-wPathobiont-induced suppressive immune imprints thwart T cell vaccine responsesIrshad Ahmed Hajam0Chih-Ming Tsai1Cesia Gonzalez2Juan Raphael Caldera3María Lázaro Díez4Xin Du5April Aralar6Brian Lin7William Duong8George Y. Liu9Department of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoAbstract Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4+ T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4+ T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4+ T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4+ T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development.https://doi.org/10.1038/s41467-024-54644-w |
| spellingShingle | Irshad Ahmed Hajam Chih-Ming Tsai Cesia Gonzalez Juan Raphael Caldera María Lázaro Díez Xin Du April Aralar Brian Lin William Duong George Y. Liu Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses Nature Communications |
| title | Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses |
| title_full | Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses |
| title_fullStr | Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses |
| title_full_unstemmed | Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses |
| title_short | Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses |
| title_sort | pathobiont induced suppressive immune imprints thwart t cell vaccine responses |
| url | https://doi.org/10.1038/s41467-024-54644-w |
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