AUTHOR=Khaw Yee Ming , Aggarwal Nupur , Barclay William E. , Kang Eunjoo , Inoue Makoto , Shinohara Mari L. 

TITLE=Th1-Dependent Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome Model With Brain Damage

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.529219

DOI=10.3389/fimmu.2020.529219

ISSN=1664-3224

ABSTRACT=<p><italic>Cryptococcus</italic>-associated immune reconstitution inflammatory syndrome (C-IRIS) is identified upon immune reconstitution in immunocompromised patients, who have previously contracted an infection of <italic>Cryptococcus neoformans</italic> (<italic>Cn</italic>). 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 <italic>Cn</italic> 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<sup>+</sup> T cells in immunocompromised <italic>Rag1</italic>-deficient mice infected with a low inoculum of <italic>Cn.</italic> 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.</p>