title: Enhanced pro-inflammatory chemokine/cytokine response triggered by pathogenic Entamoeba histolytica : basis of invasive disease.
abstract: The virulence of Entamoeba histolytica is governed by adhesion/colonization in the gut which is mediated by a galactose specific lectin. Two morphologically identical but distinct species i.e. pathogenic E. histolytica and non-pathogenic E. dispar, can be differentiated by distinct epitopes in the lectin. Both species bind to colonic epithelial cells, but only E. histolytica infection induces an inflammatory response and subsequent pathogenesis. Thus, comparing the responses of the intestinal cells to pathogenic and non-pathogenic lectins is a point of interest. The pathogenic lectin causes cytolysis of epithelial and immune-competent cells. Our data (both qualitative and mRNA quantitation) indicate that the epithelial cells responded to E. histolytica lectin with an increased expression of pro-inflammatory IL-2, IL-6, IL-8, MIP-1alpha, MCP-1, RANTES, GROalpha and GMCSF as compared to E. dispar lectin. The pathogenic LCM induced a significant increase in intracellular calcium concentration, proliferative response and chemotaxis of lymphocytes from ALA patients as compared to non-pathogenic LCM. High RANTES and IL-6 were induced in patients' lymphocytes by pathogenic LCM, along with their receptors CCR5 and CD126 as compared to NP-LCM. The local release of such a complex network of cytokines/chemokines could explain the histopathology of E. histolytica infection. The comparative low levels of these chemokines/pro-inflammatory cytokines and high levels of anti-inflammatory IL-10 in response to non-pathogenic E. dispar could explain the absence of an acute inflammatory response and the disease process. The cytokines and chemokines may provide a mechanism for initiation, amplification or containment of inflammation during disease state.
authors.affiliation: Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh - 160 012, India.
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: H
authors.initials: H
authors.lastname: Vohra
authors.forename: D
authors.initials: D
authors.lastname: Bhasin
mesh_terms: D000372:Agglutination Tests / Q000379:methods; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000302:isolation & purification / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D018925:Chemokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004748:Entamoeba histolytica / Q000276:immunology* / Q000472:pathogenicity*; D004749:Entamoebiasis / Q000276:immunology* / Q000469:parasitology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000469:parasitology; D037102:Lectins / Q000302:isolation & purification / Q000494:pharmacology; D008101:Liver Abscess, Amebic; D008214:Lymphocytes / Q000737:chemistry / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000378:metabolism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D018925:Chemokines; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D016207:Cytokines; D037102:Lectins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; C016467:Thomsen-Friedenreich antigen; D002118:Calcium