{"doi":"10.4049/jimmunol.2000159","title":"IL-1R Regulates Disease Tolerance and Cachexia in <i>Toxoplasma gondii</i> Infection","abstract":"Abstract Toxoplasma gondii is an obligate intracellular parasite that establishes life-long infection in a wide range of hosts, including humans and rodents. To establish a chronic infection, pathogens often exploit the trade-off between resistance mechanisms, which promote inflammation and kill microbes, and tolerance mechanisms, which mitigate inflammatory stress. Signaling through the type I IL-1R has recently been shown to control disease tolerance pathways in endotoxemia and Salmonella infection. However, the role of the IL-1 axis in T. gondii infection is unclear. In this study we show that IL-1R−/− mice can control T. gondii burden throughout infection. Compared with wild-type mice, IL-1R−/− mice have more severe liver and adipose tissue pathology during acute infection, consistent with a role in acute disease tolerance. Surprisingly, IL-1R−/− mice had better long-term survival than wild-type mice during chronic infection. This was due to the ability of IL-1R−/− mice to recover from cachexia, an immune-metabolic disease of muscle wasting that impairs fitness of wild-type mice. Together, our data indicate a role for IL-1R as a regulator of host homeostasis and point to cachexia as a cost of long-term reliance on IL-1–mediated tolerance mechanisms.","journal":"The Journal of Immunology","year":2020,"id":99158,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"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":408132,"name":"Claire M. Saunders","orcid":null,"position":1,"is_corresponding":false},{"id":407048,"name":"Imani Sanders","orcid":"0000-0002-3595-9129","position":2,"is_corresponding":false},{"id":407046,"name":"Jessica A. Hatter","orcid":"0000-0003-2550-4291","position":3,"is_corresponding":false},{"id":408133,"name":"Kari A. Byrnes","orcid":null,"position":4,"is_corresponding":false},{"id":350009,"name":"Sheryl Coutermarsh‐Ott","orcid":"0000-0001-7385-3969","position":5,"is_corresponding":false},{"id":407050,"name":"Sarah E. Ewald","orcid":"0000-0002-5327-7578","position":6,"is_corresponding":false},{"id":407045,"name":"Stephanie Melchor","orcid":"0000-0003-3922-3394","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T22:37:35.547042Z","pmid":"32350081","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":[]}