Bacillus anthracis, the causative agent of anthrax, secretes lethal toxin that down-regulates immune functions. Translocation of B. anthracis across mucosal epithelia is key for its dissemination and pathogenesis. Group 3 innate lymphocytes (ILC3s) are important in mucosal barrier maintenance due to their expression of the cytokine IL-22, a critical regulator of tissue responses and repair during homeostasis and inflammation. We found that B. anthracis lethal toxin perturbed ILC3 function in vitro and in vivo, revealing an unknown IL-23-mediated MAPK signaling pathway. Lethal toxin had no effects on the canonical STAT3-mediated IL-23 signaling pathway. Rather lethal toxin triggered the loss of several MAP2K kinases, which correlated with reduced activation of downstream ERK1/2 and p38, respectively. Inhibition studies showed the importance of MAPK signaling in IL-23-mediated production of IL-22. Our finding that MAPK signaling is required for optimal IL-22 production in ILC3s may lead to new approaches for targeting IL-22 biology.

炭疽杆菌是炭疽病的病原体，它分泌致命的毒素，下调免疫功能。 B的易位。炭疽病穿过粘膜上皮是其传播和发病机制的关键。第 3 组先天淋巴细胞 (ILC3) 由于表达细胞因子 IL-22（体内平衡和炎症过程中组织反应和修复的关键调节剂）而在粘膜屏障维护中发挥重要作用。我们发现B .炭疽致死毒素在体外和体内扰乱了 ILC3 功能，揭示了未知的 IL-23 介导的 MAPK 信号通路。致死毒素对经典 STAT3 介导的 IL-23 信号通路没有影响。相当致命的毒素引发了几种 MAP2K 激酶的丢失，这分别与下游 ERK1/2 和 p38 的激活减少相关。抑制研究表明 MAPK 信号传导在 IL-23 介导的 IL-22 产生中的重要性。我们发现 ILC3 中最佳 IL-22 生成需要 MAPK 信号传导，这可能会带来针对 IL-22 生物学的新方法。