1. Th1-Dependent Cryptococcus -Associated Immune Reconstitution Inflammatory Syndrome Model With Brain Damage.
- Author
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Khaw YM, Aggarwal N, Barclay WE, Kang E, Inoue M, and Shinohara ML
- Subjects
- Animals, Cryptococcosis genetics, Cryptococcosis pathology, Disease Models, Animal, Immune Reconstitution Inflammatory Syndrome, Mice, Mice, Knockout, Th1 Cells pathology, Cryptococcosis immunology, Cryptococcus neoformans immunology, Th1 Cells immunology
- Abstract
Cryptococcus -associated immune reconstitution inflammatory syndrome (C-IRIS) is identified upon immune reconstitution in immunocompromised patients, who have previously contracted an infection of Cryptococcus neoformans ( Cn ). C-IRIS can be lethal but how the immune system triggers life-threatening outcomes in patients is still poorly understood. Here, we establish a mouse model for C-IRIS with Cn serotype A strain H99, which is highly virulent and the most intensively studied. C-IRIS in mice is induced by the adoptive transfer of CD4
+ T cells in immunocompromised Rag1 -deficient mice infected with a low inoculum of Cn. The mice with C-IRIS exhibit symptoms which mimic clinical presentations of C-IRIS. This C-IRIS model is Th1-dependent and shows host mortality. This model is characterized with minimal lung injury, but infiltration of Th1 cells in the brain. C-IRIS mice also exhibited brain swelling with resemblance to edema and upregulation of aquaporin-4, a critical protein that regulates water flux in the brain in a Th1-dependent fashion. Our C-IRIS model may be used to advance our understanding of the paradoxical inflammatory phenomenon of C-IRIS in the context of neuroinflammation., (Copyright © 2020 Khaw, Aggarwal, Barclay, Kang, Inoue and Shinohara.)- Published
- 2020
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