Entamoeba histolytica trophozoites induce an inflammatory cytokine response by cultured human cells through the paracrine action of cytolytically released interleukin-1 alpha.

Abstract

Infection with the protozoan parasite Entamoeba histolytica results in a high mortality worldwide. To initiate infection, E. histolytica trophozoites in the bowel lumen penetrate the epithelium, and cause extensive lysis of host cells. The acute amebic lesions in animal models are characterized by infiltration with inflammatory cells, particularly neutrophils. The acute host response is likely important for determining whether the infection will spread systemically, but little is known regarding the signals which initiate an acute inflammatory response to E. histolytica. In the studies reported herein, we used an in vitro model system to define the proinflammatory signals produced by epithelial and other host cells in response to infection with E. histolytica trophozoites. Coculture of human epithelial and stromal cells and cell lines with trophozoites is shown to increase expression and secretion of an array of chemoattractant and proinflammatory cytokines, including IL-8, GROa, GM-CSF, IL-la, and IL-6. Moreover, high-level secretion of those cytokines is regulated by the paracrine action of cytolytically released IL-la. A second mechanism for trophozoite-induced IL-8 production involves trophozoite-target cell contact via a galactose-inhibitable amebic adherence protein, and appears to be mediated through increased intracellular calcium levels. These studies define novel mechanisms through which acute inflammation can be initiated in the host in response to a cytolytic pathogen, such as E. histolytica. (J. Clin. Invest.

Cytokine Genes are Down‐Regulated When Attachment of Entamoeba histolytica to HT‐29 Colon Epithelial Cells is Prevented

“…histolytica trophozoites induced expression of proinflammatory cytokines such as IL-8, IL-1a/b and GM-CSF from HT-29 human colonic epithelial cells. These results are compatible with the previously published report by Eckmann et al [3]. The cytokines in the present study are proinflammatory, and could recruit inflammatory cells, including PMNs and monocytes.…”

“…Eckmann et al [3] have reported narrow dose-response curves for E. histolytica stimulation of IL-8 secretion; this was also the case with IL-8 mRNA expression in this study. As shown in Table 1, increased IL-8 expression occurred in a dose-dependent manner.…”

Chlamydia trachomatis Infection of Epithelial Cells Induces the Activation of Caspase-1 and Release of Mature IL-18

“…Several reports have suggested that proinflammatory cytokines can be released from infected epithelial cells following host cell lysis after infection (27)(28)(29). Chlamydiae replicate in a specialized vacuole in the host cell cytoplasm and induce host cell lysis at the end of its developmental cycle (30).…”

“…Little is known of how a microbial pathogen might regulate IL-18 secretion from epithelial cells. IL-1␣ is an upstream cytokine that regulates the de novo production of other proinflammatory cytokines and chemokines, such as IL-8, IL-6, GM-CSF, growth-regulated oncogene-␣, and TNF-␣, from epithelial cells or endothelial cells infected with microbial pathogens such as C. trachomatis (22), Rickettsia conorii (28), Entamoeba histolytica (27), Toxoplasma gondii (29), and respiratory syncytial virus (32). Our observations demonstrate that increased IL-18 secretion in epithelial cells after C. trachomatis infection is not mediated by IL-1␣ or other secreted factor(s), indicating that IL-18 secretion from epithelial cells infected with chlamydia differs from that regulating the secretion of IL-8, IL-6, GM-CSF, TNF-␣, and other proinflammatory cytokines or chemokines.…”

Crosstalk at the initial encounter: interplay between host defense and ameba survival strategies

“…Increasing evidence indicates that IECs serve as the effectors of mucosal immune system, responding to pathogens by secretion of proinflammatory mediators and acting as antigen presenting cells (55)(56)(57). Coculture of epithelial cell lines with E. histolytica trophozoites resulted in increased production of TNF-α, IL-1α, IL-6, IL-8, GROa, and GM-CSF by the epithelial cells (57). Similar results were observed in the SCID mousehuman intestinal xenograft (SCID-Hu-INT) model, where E. histolytica infection resulted in elevated production of IL-1β and IL-8 by the human intestinal xenograft (56).…”