Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cell Rep. 2018 Mar 20;22(12):3168-3174. doi: 10.1016/j.celrep.2018.02.096.
Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida. Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice. Mice lacking both AIM2 and IFNAR2 were protected against the infection. The detrimental effects of type I IFN signaling were due to its ability to induce activation of apoptotic caspases and cell death. These results demonstrate the contrasting effects of type I IFN signaling and AIM2 during F. novicida infection in vivo and indicate a dominant role for type I IFNs in mediating detrimental responses despite the protective AIM2 inflammasome responses.
干扰素 (IFNs) 和炎性小体是抗微生物免疫的重要介质。I 型 IFN 信号通路驱动巨噬细胞中 AIM2 炎性小体的激活；然而，IFNs 和炎性小体反应在宿主防御中的相对贡献尚不清楚。我们报告了在弗氏柠檬酸杆菌感染期间缺乏 I 型 IFN 信号的小鼠中完整的 AIM2 炎性小体反应。与 AIM2 缺陷型小鼠的易感性增加相反，缺乏 I 型 IFN 信号赋予了对弗氏柠檬酸杆菌感染的保护作用。同时缺乏 AIM2 和 IFNAR2 的小鼠也能抵抗这种感染。I 型 IFN 信号的有害作用是由于其诱导凋亡半胱氨酸酶激活和细胞死亡的能力。这些结果表明，在体内弗氏柠檬酸杆菌感染期间，I 型 IFN 信号和 AIM2 具有相反的作用，并表明尽管存在保护性的 AIM2 炎性小体反应，但 I 型 IFNs 在介导有害反应方面发挥着主导作用。
