RESUMO
Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.
Assuntos
Proteína da Polipose Adenomatosa do Colo/deficiência , Proteína da Polipose Adenomatosa do Colo/metabolismo , Carcinogênese , Neoplasias do Colo/epidemiologia , Tricuríase/complicações , Trichuris/patogenicidade , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Doença Crônica , Neoplasias do Colo/etiologia , Modelos Animais de Doenças , Incidência , CamundongosRESUMO
The functional integrity of the intestinal epithelial barrier forms a major defense against invading pathogens, including gastrointestinal-dwelling nematodes, which are ubiquitous in their distribution worldwide. Here, we show that an increase in the rate of epithelial cell turnover in the large intestine acts like an "epithelial escalator" to expel Trichuris and that the rate of epithelial cell movement is under immune control by the cytokine interleukin-13 and the chemokine CXCL10. This host protective mechanism against intestinal pathogens has implications for our wider understanding of the multifunctional role played by intestinal epithelium in mucosal defense.