It has been reported that IL-33 receptor ST2 deficiency mitigates Cryptococcus neoformans (C. neoformans) pulmonary infection in BALB/c mice. IL-33 may modulate immune responses in ST2-dependent and ST2-independent manners. The host genetic background (i.e., BALB/c, C57BL/6 J) influences immune responses against C. neoformans. In the present study, we aimed to explore the roles of IL-33 and ST2 in pulmonary C. neoformans-infected mice on a C57BL/6 J genetic background. C. neoformans infection increased IL-33 expression in lung tissues. IL-33 deficiency but not ST2 deficiency significantly extended the survival time of C. neoformans-infected mice. In contrast, either IL-33 or ST2 deficiency reduced fungal burdens in lung, spleen and brain tissues from the mice following C. neoformans intratracheal inoculation. Similarly, inflammatory responses in the lung tissues were more pronounced in both the IL-33^−/− and ST2^−/− infected mice. However, mucus production was decreased in IL-33^−/− infected mice alone, and the level of IL-5 in bronchoalveolar lavage fluid (BALF) was substantially decreased in the IL-33^−/− infected mice but not ST2^−/− infected mice. Moreover, IL-33 deficiency but not ST2 deficiency increased iNOS-positive macrophages. At the early stage of infection, the reduced pulmonary fungal burden in the IL-33^−/− and ST2^−/− mice was accompanied by increased neutrophil infiltration. Collectively, IL-33 regulated pulmonary C. neoformans infection in an ST2-dependent and ST2-independent manner in C57BL/6 J mice.

据报道，IL-33 受体 ST2 缺陷可减轻BALB/c 小鼠的新型隐球菌( C. neoformans ) 肺部感染。IL-33 可能以 ST2 依赖性和 ST2 非依赖性方式调节免疫反应。宿主遗传背景（即 BALB/c、C57BL/6 J）影响针对新型隐球菌的免疫反应。在本研究中，我们旨在探讨 IL-33 和 ST2 在 C57BL/6 J 遗传背景下感染肺部新生隐球菌的小鼠中的作用。新型隐球菌感染增加了肺组织中 IL-33 的表达。IL-33 缺陷而非 ST2 缺陷显着延长了新型隐球菌的存活时间- 感染小鼠。相比之下，IL-33 或 ST2 缺陷可减少气管内接种新生隐球菌后小鼠肺、脾和脑组织中的真菌负荷。类似地，IL-33 ^-/-和 ST2 ^-/-感染小鼠的肺组织炎症反应更为明显。^{然而，仅在 IL-33 -/-}感染的小鼠中粘液产生减少，并且在 IL-33 ^-/-感染的小鼠中支气管肺泡灌洗液 (BALF) 中的 IL-5 水平显着降低，但 ST2 ^-/-没有被感染的老鼠。此外，IL-33 缺乏而非 ST2 缺乏会增加 iNOS 阳性巨噬细胞。在感染的早期阶段，IL-33 ^-/-和 ST2 ^-/-小鼠肺部真菌负荷的减少伴随着中性粒细胞浸润的增加。总的来说，IL-33在 C57BL/6 J 小鼠中以 ST2 依赖性和 ST2 非依赖性方式调节肺部新生隐球菌感染。