Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Immunity. 2011 Aug 26;35(2):249-59. doi: 10.1016/j.immuni.2011.08.008.
CD8α(+) dendritic cells (DCs) are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, secretion of interleukin-12 (IL-12) by CD8α(+) DCs suggests a role for these cells in response to Toxoplasma gondii antigens, although it remains unclear whether these cells are required for protection against T. gondii infection. Toward this goal, we examined T. gondii infection of Batf3(-/-) mice, which selectively lack only lymphoid-resident CD8α(+) DCs and related peripheral CD103(+) DCs. Batf3(-/-) mice were extremely susceptible to T. gondii infection, with decreased production of IL-12 and interferon-γ. IL-12 administration restored resistance in Batf3(-/-) mice, and mice in which IL-12 production was ablated only from CD8α(+) DCs failed to control infection. These results reveal that the function of CD8α(+) DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection.
CD8α(+)树突状细胞 (DCs) 在体内对于源自细胞内病原体和肿瘤的抗原的交叉呈递非常重要。此外，CD8α(+) DCs 分泌白细胞介素-12 (IL-12) 表明这些细胞在应对刚地弓形虫抗原时发挥作用，尽管尚不清楚这些细胞是否对于预防刚地弓形虫感染是必需的。为了实现这一目标，我们研究了 Batf3(-/-) 小鼠的刚地弓形虫感染，这些小鼠选择性地缺乏仅淋巴组织驻留的 CD8α(+) DCs 和相关的外周 CD103(+) DCs。Batf3(-/-) 小鼠对刚地弓形虫感染极其敏感，IL-12 和干扰素-γ 的产生减少。IL-12 给药恢复了 Batf3(-/-) 小鼠的抵抗力，而仅从 CD8α(+) DCs 中消除 IL-12 产生的小鼠未能控制感染。这些结果表明，CD8α(+) DCs 的功能不仅限于交叉呈递，还包括在刚地弓形虫感染期间通过产生 IL-12 激活先天免疫的关键作用。
