INNATE IMMUNE RESPONSES TO MICROBES AND ROLE IN CARCINOGENESIS (COLORECTAL CANCER)

 Figure caption: Role of Dysbiosis and Immune Dysfunctions in Colon Carcinogenesis  (A)  Dysbiosis, as a result of inflammasome deficiencies, could promote tumorigenesis. Inflammasome-derived IL-18 is necessary for tissue repair, protection against tumors, and the maintenance of the microbial ecology equilibrium. In turn, this phenotype associated with the lack of IL-18 could be exacerbated by a dysbiotic microbiota that could lead to chronic inflammation, increased IL-6 signaling, and tumorigenesis. In intestinal epithelial cells, IL-6 activates STAT3 signaling, protecting normal and premalignant cells from apoptosis.   (B)  Dysbiosis and immune dysfunctions may allow increased bacterial translocation due to altered barrier function. Microorganism-associated molecular patterns (MAMPs) are detected by Toll-like receptors (TLRs) present in epithelial cells, macrophages, and myofibroblasts, leading to the activation of different pathways that promote cancer development. Epiregulin (EREG) and amphiregulin (AREG) are epidermal growth factor receptor (EGFR) ligands and therefore induce proliferation through MAPK/ERK pathway activation. Th17 cytokines mark the early stages of CRC by induction of STAT3."  – T. Irrazábal, Molecular Cell, 2014

Technical:

Adobe Illustrator

Audience

Scientific community, researchers

Supervisors (scientific):

Dr. A Martin, T Irrazábal

Supervisors (technical):

M Corrin, Dr. L Wilson-Pauwels

PUBLICATION:

T. Irrazábal, A Balcheva, SE Girardin, A Martin, DJ Philpott, "The multifaceted role of the intestinal microbiota in colon cancer" | CELL, Molecular Cell. 2014.

Description:

[labels have been removed] Depicting the TLR and NLR pathways that are hypothesized to generate innate immune responses to microbes in the colon and its role in carcinogenesis. The goal of the illustration is to show the possibility of the two pathways, as shown in the call-outs of the intestinal epithelium.

Role of Dysbiosis and Immune Dysfunctions in Colon Carcinogenesis
(A) Dysbiosis, as a result of inflammasome deficiencies, could promote tumorigenesis. Inflammasome-derived IL-18 is necessary for tissue repair, protection against tumors, and the maintenance of the microbial ecology equilibrium. In turn, this phenotype associated with the lack of IL-18 could be exacerbated by a dysbiotic microbiota that could lead to chronic inflammation, increased IL-6 signaling, and tumorigenesis. In intestinal epithelial cells, IL-6 activates STAT3 signaling, protecting normal and premalignant cells from apoptosis. 
(B) Dysbiosis and immune dysfunctions may allow increased bacterial translocation due to altered barrier function. Microorganism-associated molecular patterns (MAMPs) are detected by Toll-like receptors (TLRs) present in epithelial cells, macrophages, and myofibroblasts, leading to the activation of different pathways that promote cancer development. Epiregulin (EREG) and amphiregulin (AREG) are epidermal growth factor receptor (EGFR) ligands and therefore induce proliferation through MAPK/ERK pathway activation. Th17 cytokines mark the early stages of CRC by induction of STAT3." 
– T. Irrazábal, Molecular Cell, 2014