Fig. 8: Schematic representation of Eh-macrophage interactions at the intercellular junction with downstream effects (altered autophagy) and outcome (enhanced inflammatory responses). | Mucosal Immunology

Fig. 8: Schematic representation of Eh-macrophage interactions at the intercellular junction with downstream effects (altered autophagy) and outcome (enhanced inflammatory responses).

From: Entamoeba histolytica exploits the autophagy pathway in macrophages to trigger inflammation in disease pathogenesis

Fig. 8

At the intercellular junction between Eh-macrophage, Eh contact with macrophage through cell surface adhesin Gal-lectin mediates high affinity binding. Simultaneously, EhCP-A1 and EhCP-A4, localized within intracellular vesicles, polarized to the Eh-macrophage contact site to activate caspase-6, which is independent of EhCP-A5. Activated caspase-6 induce degradation of the autophagy ATG16L1 protein complex composed of ATG16L1 and ATG5-ATG12 conjugate. ATG12-ATG5 conjugate formation requires ATG7, which activate ATG12 to interact with ATG5. Eh-induced active caspase-6 trigger dissociation of ATG5 protein from the ATG12-ATG5 conjugate. Eh-macrophage interaction downregulate ATG7 which can also interfere with ATG16L1-ATG12-ATG5 complex formation. ATG16L1 protein complex is vital for the downstream LC3 conjugation with phosphatidylethanolamine (PE) for autophagosome formation. In disease pathogenesis, ATG16L1 is a proteolytic substrate for Eh-activated active caspase-6 and modulate the immune regulatory process autophagy-associated proteins to potentiate the host inflammatory responses by increased secretion of TNF-α, IL-1β and IL-18 in an inflammasome independent manner.

Back to article page