FIGURE 1: TNF and CSP are two essential elements of the cascade of events which lead to amebic colitis.

(Left panel) Asymptomatic amebiasis: (1) Trophozoites are living as nonpathogenic intestinal commensals, without causing any noticeable damage to the host. (2) These trophozoites feed on bacteria and cellular debris that are present in the lumen of the colon and on the surface of the colonic mucus.

(Right panel) Symptomatic amebiasis: (3) Trophozoites degrade the mucus layer (involvement of β-amylase [4] and CP-A5 [8] in this process), trigger a host inflammatory response and induce the collagen remodeling that is required for invasion of the lamina propria (involvement of CP-A5) [9]. (4) The invasion of the colonic mucosa by E. histolytica generates an acute pro-inflammatory reaction which is characterized by the recruitment of macrophages and the production of the pro-inflammatory cytokines, such as TNF. (5) Inflammation causes change in the gastrointestinal microbiota [16] and this new flora may be less favorable to the parasite growth. (6) The parasite is attracted to the source of TNF production and CSP is essential for this process. (7) TNF increase vascular endothelial permeability [18] and consequently provides the parasite with an access to erythrocytes. These erythrocytes may represent a better source of nutriment for the parasite than the bacterial flora that is associated with colitis.

4. Thibeaux R, Weber C, Hon CC, Dillies MA, Ave P, Coppee JY, Labruyere E, Guillen N. (2013). Identification of the Virulence Landscape Essential for Entamoeba histolytica Invasion of the Human Colon. PLoS Pathog 9:e1003824.

8. Kissoon-Singh V, Moreau F, Trusevych E, Chadee K. (2013). Entamoeba histolytica exacerbates epithelial tight junction permeability and proinflammatory responses in Muc2(-/-) mice. Am J Pathol 182:852-865.

9. Thibeaux R, Ave P, Bernier M, Morcelet M, Frileux P, Guillen N, Labruyere E. (2014). The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue. Nat Commun 5:5142.

16. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. (2007). Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104:13780-13785.

18. Royall JA, Berkow RL, Beckman JS, Cunningham MK, Matalon S, Freeman BA. (1989). Tumor necrosis factor and interleukin 1 alpha increase vascular endothelial permeability. Am J Physiol 257:L399-410.

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