Differential induction of immunoregulatory circuits of phagocytic cells by Gal/Gal NAc lectin from pathogenic and nonpathogenic Entamoeba.
BACKGROUND
Amoebic liver abscess (ALA) is an acute inflammatory disease caused by Entamoeba histolytica.


METHODS
The key player in the pathogenesis and immunoprotection is the Gal/GalNAc inhibitable lectin, possessed by both pathogenic (Entamoeba histolytica) and nonpathogenic (Entamoeba dispar) strains, but only E. histolytica infection is associated with an acute inflammation and subsequently the disease.


CONCLUSIONS
The stimulation with the lectin induces the secretion of various proinflammatory cytokines/chemokines from intestinal epithelial cells. The differential induction of cytokine/chemokine network by the two strains can further regulate the immunoregulatory functions of the immune cells (monocytes and neutrophils) of the host. The soluble levels of IL-1beta, IL-6, IL-8, IL-10, MIP-1alpha, MCP-1, RANTES, GRO-alpha, GMCSF were quantitated to be significantly higher in pathogenic lectin-induced conditioned media (LCM) compared to nonpathogenic LCM (NP-LCM). The monocytes from ALA patients responded to the presence of pathogenic-LCM (P-LCM) by lowering of intracellular Ca(2+) (which was still higher than control). The proinflammatory MCP-1, GRO-alpha, and GMCSF levels in the monocytes were recorded both (quantitatively and mRNA quantitation) to be tremendously higher along with their respective receptors, with P-LCM compared to NP-LCM. A significant increase in the reactive oxygen intermediates and chemotactic index (CI) was observed in the monocytes when treated with P-LCM. Similarly, in neutrophils of ALA patients, an increase in intracellular Ca(2+), ROS and chemotaxis was observed with P-LCM.


OBJECTIVE
The study is a step towards understanding the mechanism of immunopathogenesis of amoebiasis, on one hand, and points to the central role of cytokine/chemokine network in the process, on the other hand.
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh 160 012, India. monika_sharma540@yahoo.com
Monika
M
Sharma
Deepak
D
Bhasin
Harpreet
H
Vohra
D000208:Acute Disease; D000818:Animals; D001212:Asialoglycoproteins / Q000494:pharmacology*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000032:analysis; D016207:Cytokines / Q000378:metabolism*; D004705:Endocytosis; D004748:Entamoeba histolytica / Q000472:pathogenicity*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D037102:Lectins / Q000494:pharmacology; D008101:Liver Abscess, Amebic / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D014774:Virulence / Q000276:immunology
D001212:Asialoglycoproteins; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D037102:Lectins