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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\u2212\/\u2212 mice can control T. gondii burden throughout infection. Compared with wild-type mice, IL-1R\u2212\/\u2212 mice have more severe liver and adipose tissue pathology during acute infection, consistent with a role in acute disease tolerance. Surprisingly, IL-1R\u2212\/\u2212 mice had better long-term survival than wild-type mice during chronic infection. This was due to the ability of IL-1R\u2212\/\u2212 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\u2013mediated tolerance mechanisms.<\/jats:p>","DOI":"10.4049\/jimmunol.2000159","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T22:12:30Z","timestamp":1588198350000},"page":"3329-3338","source":"Crossref","is-referenced-by-count":31,"title":["IL-1R Regulates Disease Tolerance and Cachexia in <i>Toxoplasma gondii<\/i> Infection"],"prefix":"10.1093","volume":"204","author":[{"given":"Stephanie J","family":"Melchor","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine , Charlottesville, VA 22908"},{"name":"The Carter Immunology Center, University of Virginia School of Medicine , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M","family":"Saunders","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine , Charlottesville, VA 22908"},{"name":"The Carter Immunology Center, University of Virginia School of Medicine , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3595-9129","authenticated-orcid":false,"given":"Imani","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine , Charlottesville, VA 22908"},{"name":"The Carter Immunology Center, University of Virginia School of Medicine , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2550-4291","authenticated-orcid":false,"given":"Jessica A","family":"Hatter","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Virginia School of Medicine , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari A","family":"Byrnes","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine , Charlottesville, VA 22908"},{"name":"The Carter Immunology Center, University of Virginia School of Medicine , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-3969","authenticated-orcid":false,"given":"Sheryl","family":"Coutermarsh-Ott","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine , Blacksburg, VA 24060"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5327-7578","authenticated-orcid":false,"given":"Sarah E","family":"Ewald","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine , Charlottesville, VA 22908"},{"name":"The Carter Immunology Center, University of Virginia School of Medicine , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2025030417512223700_r1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0090203","article-title":"Toxoplasmosis--a global threat. 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