| First Author | Melchor SJ | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 12 | Pages | 3329-3338 |
| PubMed ID | 32350081 | Mgi Jnum | J:292582 |
| Mgi Id | MGI:6445061 | Doi | 10.4049/jimmunol.2000159 |
| Citation | Melchor SJ, et al. (2020) IL-1R Regulates Disease Tolerance and Cachexia in Toxoplasma gondii Infection. J Immunol 204(12):3329-3338 |
| abstractText | 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. |
