Chemotaxis ofEntamoeba histolyticatowards the pro-inflammatory cytokine TNF is based on PI3K signalling, cytoskeleton reorganization and the GalactoseN-acetylgalactosamine lectin activity

Abstract

SummaryEntamoeba histolytica is the protozoan parasite responsible for human amoebiasis. During invasive amoebiasis, migration is an essential process and it has previously been shown that the pro-inflammatory compound tumour necrosis factor (TNF) is produced and that it has a migratory effect on E. histolytica. This paper focuses on the analysis of parasite signalling and cytoskeleton changes leading to directional motility. TNF-induced signalling was PI3K-dependent and could lead to modifications in the polarization of certain cytoskeleton-related proteins. To analyse the effect of TNF signalling on gene expression, we used microarray analysis to screen for genes encoding proteins that were potentially important during chemotaxis towards TNF. Interestingly, we found that elements of the galactose/N-acetylgalactosamine lectin (Gal/GalNAc lectin) were upregulated during chemotaxis as well as genes encoding proteins involved in cytoskeleton dynamics. The a-actinin protein appeared to be an important candidate to link the Gal/GalNAc lectin to the cytoskeleton during chemotaxis signalling. Dominant negative parasites blocked for Gal/GalNAc lectin signalling were no longer able to chemotax towards TNF. These results have given us an insight on how E. histolytica changes its cytoskeleton dynamics during chemotaxis and revealed the capital role of PI3K and Gal/GalNAc lectin signalling in chemotaxis.

The Macrophage Migration Inhibitory Factor Homolog of Entamoeba histolytica Binds to and Immunomodulates Host Macrophages

“…It has been shown that TNF-␣ has a chemotactic effect on E. histolytica; hence, it is possible that by enhancing TNF-␣, EhMIF promotes parasite invasion (57,58). Also, TNF-␣ promotes adherence of E. histolytica to host cells (59).…”

Protein Kinases of the Parasitic ProtistEntamoeba histolytica

“…Only a few cell surface-initiated, ligand-induced signaling pathways have been documented, examples being the initiation of phagocytosis [32,33], chemotactic response [34], and fibronectin-induced cytoskeleton reorganization [35]. Although several putative cell-surface receptors, such as a 170 kDa Gal/GalNAc lectin (a laminin receptor) and LECAM3 (a homolog of the leukocyte adhesion molecule) have been identified, signaling pathways that function via these molecules have not yet been elucidated [36].…”

Tyrosine phosphorylation/dephosphorylation of myosin II essential light chains of Entamoeba histolytica trophozoites regulates their motility

“…Motile responses of Entamoebahistolytica trophozoites to specific stimuli are important factors not only for their survival in the human intestine as commensals, but also for their activities as invasive pathogens [1][2][3][4][5].…”