Mao Haitong, Dumas Eric K, Starnbach Michael N
1Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.
Infect Immun. 2025 Feb 18;93(2):e0040224. doi: 10.1128/iai.00402-24. Epub 2025 Jan 8.
The lack of effective adaptive immunity against leads to chronic or repeated infection and serious disease sequelae. Dendritic cells (DCs) are professional antigen-presenting cells that are crucial for the activation of T cells during infection. cDC1s and cDC2s are the two main DC subsets responsible for T cell priming, but little is known about how affects their ability to prime T cells. Using a mouse model of infection, we found that uptake reduced the viability of cDC1s and cDC2s both and , with cDC1s experiencing more death. DC death was mainly due to apoptosis and is alleviated in or knockout DCs. In addition, we observed that -specific CD8+ T cells were preferentially activated by cDC1s. Reduction in DC viability by impaired the ability of infected DCs to activate T cells upon co-culture, although in the case of CD8+ T cell priming, controlling for viability was insufficient to fully rescue the defect. RNA sequencing of DCs from infected mice showed upregulation of cell death pathways, supporting our observations of DC death caused by . Finally, we validated our findings with human DCs , observing -induced cell death. These results indicate that may evade the adaptive immune system by directly inducing cell death in DCs.
缺乏针对……的有效适应性免疫会导致慢性或反复感染以及严重的疾病后遗症。树突状细胞（DCs）是专职抗原呈递细胞，在……感染期间对T细胞的激活至关重要。cDC1s和cDC2s是负责T细胞致敏的两个主要DC亚群，但关于……如何影响它们致敏T细胞的能力知之甚少。利用感染小鼠模型，我们发现……摄取降低了cDC1s和cDC2s在……和……时的活力，其中cDC1s死亡更多。DC死亡主要是由于细胞凋亡，并且在……或……基因敲除的DC中有所缓解。此外，我们观察到……特异性CD8 + T细胞优先被cDC1s激活。……导致的DC活力降低损害了感染的DC在共培养时激活T细胞的能力，尽管在CD8 + T细胞致敏的情况下，控制活力不足以完全挽救缺陷。对感染小鼠的DC进行RNA测序显示细胞死亡途径上调，支持了我们关于……导致DC死亡的观察结果。最后，我们用人DC验证了我们的发现，观察到……诱导的细胞死亡。这些结果表明……可能通过直接诱导DC细胞死亡来逃避适应性免疫系统。
