A comparative study of IL-33 and its receptor ST2 in a C57BL/6 J mouse model of pulmonary Cryptococcus neoformans infection.

Zhengxia Wang, Qiyun Ma, Jingxian Jiang, Xiaofan Yang, Enrui Zhang, Yuan Tao, Huidi Hu, Mao Huang, Ningfei Ji, Mingshun Zhang

Medical microbiology and immunology 2023 Feb

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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. © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Zhengxia Wang, Qiyun Ma, Jingxian Jiang, Xiaofan Yang, Enrui Zhang, Yuan Tao, Huidi Hu, Mao Huang, Ningfei Ji, Mingshun Zhang. A comparative study of IL-33 and its receptor ST2 in a C57BL/6 J mouse model of pulmonary Cryptococcus neoformans infection. Medical microbiology and immunology. 2023 Feb;212(1):53-63