{"doi":"10.3389/fimmu.2020.529219","title":"Th1-Dependent Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome Model With Brain Damage","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 inflammation, 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.","journal":"Frontiers in Immunology","year":2020,"id":105756,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9447,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":511470,"name":"Nupur Aggarwal","orcid":"0000-0002-7992-0023","position":1,"is_corresponding":false},{"id":511471,"name":"William E. Barclay","orcid":"0000-0002-6910-9157","position":2,"is_corresponding":false},{"id":511807,"name":"Eunjoo Kang","orcid":null,"position":3,"is_corresponding":false},{"id":511472,"name":"Makoto Inoue","orcid":"0000-0002-3991-3806","position":4,"is_corresponding":false},{"id":249988,"name":"Mari L. Shinohara","orcid":"0000-0002-6808-9844","position":5,"is_corresponding":false},{"id":511469,"name":"Yee Ming Khaw","orcid":"0000-0003-2452-3968","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:12:21.275494Z","pmid":"33133067","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}