Toxoplasma gondii infection triggers chronic cachexia and sustained commensal dysbiosis in mice.
Jessica A HatterYue Moi KoucheStephanie J MelchorKatherine NgDonna M BouleyJohn C BoothroydSarah E EwaldPublished in: PloS one (2018)
Toxoplasma gondii is a protozoan parasite with a predation-mediated transmission cycle between rodents and felines. Intermediate hosts acquire Toxoplasma by eating parasite cysts which invade the small intestine, disseminate systemically and finally establish host life-long chronic infection in brain and muscles. Here we show that Toxoplasma infection can trigger a severe form of sustained cachexia: a disease of progressive lean weight loss that is a causal predictor of mortality in cancer, chronic disease and many infections. Toxoplasma cachexia is characterized by acute anorexia, systemic inflammation and loss of 20% body mass. Although mice recover from symptoms of peak sickness, they fail to regain muscle mass or visceral adipose depots. We asked whether the damage to the intestinal microenvironment observed at acute time points was sustained in chronic infection and could thereby play a role in sustaining cachexia. We found that parasites replicate in the same region of the distal jejunum/proximal ileum throughout acute infection, inducing the development of secondary lymphoid structures and severe, regional inflammation. Small intestine pathology was resolved by 5 weeks post-infection. However, changes in the commensal populations, notably an outgrowth of Clostridia spp., were sustained in chronic infection. Importantly, uninfected animals co-housed with infected mice display similar changes in commensal microflora but never display symptoms of cachexia, indicating that altered commensals are not sufficient to explain the cachexia phenotype alone. These studies indicate that Toxoplasma infection is a novel and robust model to study the immune-metabolic interactions that contribute to chronic cachexia development, pathology and potential reversal.
Keyphrases
- toxoplasma gondii
- weight loss
- drug induced
- oxidative stress
- liver failure
- stem cells
- multiple sclerosis
- bariatric surgery
- early onset
- skeletal muscle
- type diabetes
- insulin resistance
- respiratory failure
- cardiovascular disease
- mass spectrometry
- squamous cell carcinoma
- young adults
- gastric bypass
- cardiovascular events
- extracorporeal membrane oxygenation
- body mass index
- cerebral ischemia
- papillary thyroid
- minimally invasive