Extraintestinal Helminth Infection Reduces the Development of Colitis-Associated Tumorigenesis

Abstract

Colitis-associated colorectal cancer (CAC) is one of the most common cancers and is closely related to chronic or deregulated inflammation. Helminthic infections can modulate inflammatory responses in some diseases, but their immunomodulatory role during cancer development remains completely unknown. We have analyzed the role of Taenia crassiceps-induced anti-inflammatory response in determining the outcome of CAC. We show that extraintestinal T. crassiceps infection in CAC mice inhibited colonic inflammatory responses and tumor formation and prevented goblet cell loss. There was also increased expression of IL-4 and alternatively activated macrophages markers in colonic tissue and negative immunomodulation of pro-inflammatory cytokine expression. In addition, T. crassiceps infection prevented the upregulation of β-catenin and CXCR2 expression observed in the CAC mice, which are both markers associated with CAC-tumorigenesis, and reduced the numbers of circulating and colonic CD11b+Ly6ChiCCR2+ monocytes. Thus, immunomodulatory activities induced by helminth infections may have a role in the progression of CAC.

Regulation of immunity by Taeniids: lessons from animal models and in vitro studies

“…We know that chronic and unregulated inflammatory responses are now considered to be another hallmark for carcinogenesis , and as shown here, Taeniids can induce a battery of anti‐inflammatory mechanisms that may modulate some inflammatory diseases. Chronic inflammation is involved in colonic carcinogenesis and we found that T. crassiceps infection significantly reduces the number of tumours and the progression of colonic carcinogenesis, which was associated with the prevention of goblet cells loss, a decrease in histological alterations and a negative immunomodulation of the expression of the pro‐inflammatory cytokines TNF‐α and IFN‐γ, whereas a positive immunomodulatory effect of AAM expression markers was observed . In sharp divergence, downregulated tumour immunity by E. granulosus infection greatly favoured cancer metastasis to the liver in a breast tumour model , where a significant expansion of Tregs was involved.…”

Helminth‐derived molecules inhibit colitis‐associated colon cancer development through NF‐κB and STAT3 regulation

“…For histological analysis, longitudinal sections from the large intestine were immediately fixed according to previously described protocols . Colon sections with a thickness of 5 μm were stained with hematoxylin and eosin (H&E) to visualize cell morphology or with alcian blue to visualize goblet cells using an optical microscope (Axio Vert.…”

“…Nonetheless, the mechanisms of action triggered by parasites in modulating cancer development are diverse and incompletely described. Our previous work indicated that preinfection with Taenia crassiceps (a helminth) reduced the development of CAC . However, the roles played by molecules excreted/secreted by T. crassiceps (TcES) in the development of CAC are unknown.…”

Chronic infections with viruses or parasites: breaking bad to make good

“…Infection with the extraintestinal tapeworm Taenia crassiceps reduced the development of colitis‐associated tumours in a murine model of colorectal cancer. This effect was associated with increased expression of the type 2 cytokine IL‐4 and with alterations in innate immunity, including macrophage alternative activation, neutrophil attraction and the recruitment of inflammatory monocytes …”

“…This effect was associated with increased expression of the type 2 cytokine IL-4 and with alterations in innate immunity, including macrophage alternative activation, neutrophil attraction and the recruitment of inflammatory monocytes. 73 In a similar manner to chronic viral infections, helminths have evolved potent mechanisms to regulate the host immune response, in order to ensure their long-term survival. 74 As well as notable effects on specific anti-parasite responses, helminth immune regulation is proposed to exert mutualistic symbiosis, similar to the chronic viral infections discussed in the previous section, to further benefit the hostby suppressing responses to a number of allergens and autoantigens.…”