Congratulations Stephanie Melchor!

July 14, 2020 by sww2p@virginia.edu

In May, Stephanie Melchor successfully defended her thesis, “IL-1R drives acute disease tolerance, liver and skeletal muscle fibrosis, and sustained cachexia during T. gondii infection.” During her work in Sarah Ewald’s lab, Stephanie helped characterize the muscle and adipose tissue wasting that occurs in mice during chronic infection with Toxoplasma gondii (T. gondii) as cachexia, a deadly muscle wasting disease associated with most chronic human illness. This discovery is a critical tool for the cachexia field, as it introduces a natural infection model that allows for mechanisms of wasting to be studied over the course of months rather than days to weeks (the span of most popular experimental models of cachexia today). Stephanie’s worked helped show that T. gondii-induced cachexia is dependent on intact signaling through the type 1 IL-1 receptor (IL-1R). Importantly, while IL-1R signaling is dispensable for control of the parasite, it promotes pathways of disease tissue tolerance in the liver and adipose tissue during acute infection. In addition to cachexia, IL-1R is also necessary for the perivascular fibrosis that arises in the skeletal muscle and liver of cachectic mice, a heretofore unobserved phenomenon in experimental cachexia models, despite being seen in clinical cachexia.