Hajam Irshad Ahmed, Tsai Chih-Ming, Gonzalez Cesia, Caldera Juan Raphael, Lázaro Díez María, Du Xin, Aralar April, Lin Brian, Duong William, Liu George Y
Department of Pediatrics, University of California San Diego, San Diego, CA, 92093, USA.
Quest Diagnostics, 33608 Ortega Hwy., San Juan Capistrano, CA, 92675, USA.
Nat Commun. 2024 Dec 16;15(1):10335. doi: 10.1038/s41467-024-54644-w.
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.
致病共生菌已经进化出许多与宿主共存的策略，但免疫逃避机制如何导致针对致病共生菌的疫苗研发困难尚不清楚。与此同时，金黄色葡萄球菌（SA）迄今为止一直阻碍着人类疫苗的研发。在此我们表明，先前接触SA会诱导产生非保护性CD4 T细胞印记，导致对保护性IsdB疫苗反应的减弱。从机制上讲，这些经历过SA的CD4 T细胞表达IL-10，而IL-10会因接种疫苗而进一步扩增，并通过与CD4 T细胞上的IL-10Rα结合来阻碍疫苗保护，并抑制IL-17A的产生。IL-10还介导对IsdB和sdrE多抗原疫苗的交叉抑制。相比之下，SA的IsdB、IsdA和MntC疫苗的低效性可通过与促进IL-17A和IFN-γ反应的佐剂联合治疗来克服。因此，我们提出，分泌IL-10的、经历过SA的CD4 T细胞印记代表了一种葡萄球菌免疫逃逸机制，这在未来疫苗研发中需要加以考虑。
