ena-STUDY-UNIVERSITY OF BRITISH COLUMBIA-02-03-2018-21:13:33:781-2185
This project consists of four experiments which test the effect of DNBS-induced colitis on rats hosting the tapeworm H. diminuta in both the pre-patent and patent periods of the helminth's life cycle. The studies examine the 16s microbial community during the infection and colitis-induction processes.
Hymenolepis diminuta infection in rats is an attractive model for a therapeutic helminthbecause the long-term and stable infection resembles the long-term associations humanshistorically had with helminths and offers the possibility of long-term treatment. Here weinvestigate the ability of H. diminuta to protect rats against colitis induced through applicationof the haptenizing agent DNBS directly to the colon. We test the ability of immature H.diminuta to ameliorate the effects of colitis during the prepatent period, when H. diminutainduces a type 2 immune response. We also test mature H. diminuta (patent period) againstboth moderate (single DNBS application) and severe (two DNBS applications) colitis, a modeldeveloped in this study to assess the effects of H. diminuta on longer-term disease. We monitorthe gut bacterial microbiota over time, as well as measures of rat health and TNFa expression.We show that mature H. diminuta results in lower inflammation, faster recovery and lesserpathology from severe colitis, but has little impact on moderate colitis. Immature H. diminutainduce elevated IL-10 expression, but do not protect against severe colitis. The gut microbiotais disrupted during colitis and does not appear to play an overt role in H. diminuta mediatedprotection.
Hymenolepis diminuta infection in rats is an attractive model for a therapeutic helminthbecause the long-term and stable infection resembles the long-term associations humanshistorically had with helminths and offers the possibility of long-term treatment. Here weinvestigate the ability of H. diminuta to protect rats against colitis induced through applicationof the haptenizing agent DNBS directly to the colon. We test the ability of immature H.diminuta to ameliorate the effects of colitis during the prepatent period, when H. diminutainduces a type 2 immune response. We also test mature H. diminuta (patent period) againstboth moderate (single DNBS application) and severe (two DNBS applications) colitis, a modeldeveloped in this study to assess the effects of H. diminuta on longer-term disease. We monitorthe gut bacterial microbiota over time, as well as measures of rat health and TNFa expression.We show that mature H. diminuta results in lower inflammation, faster recovery and lesserpathology from severe colitis, but has little impact on moderate colitis. Immature H. diminutainduce elevated IL-10 expression, but do not protect against severe colitis. The gut microbiotais disrupted during colitis and does not appear to play an overt role in H. diminuta mediatedprotection.