Effective human defense against E. histolytica: high amoebicidal activity of lymphocytes and monocytes in amoebic liver abscess patients until 3 months follow-up

Vohra, Harpreet; Kaur, Upninder; Sharma, Animesh; Bhalla, Veena; Bhasin, Deepak K.

doi:10.1016/s1383-5769(03)00025-4

Cited by 11 publications

(9 citation statements)

References 9 publications

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“…In contrast to prior studies with PHA [20, 21], stimulation with antigens from E. histolytica was found to augment binding intensity of T cells to the trophozoites rather than the binding frequency [22]. Thus, the more important determinants in killing amoeba may be the binding characteristics of the CTL rather than the number of CTL bound.…”

Section: Direct Killing Of Parasites By Ctlmentioning

confidence: 57%

“…First, with rare exceptions, killing is contact-dependent. Several studies reported a correlation between the frequency [20, 21] or intensity [22] of binding and killing. Moreover, microscopy [37, 40, 41] revealed direct CTL-microbe interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Specific activation of T cells isolated from patients with an amoebic liver abscess with an E. histolytica lysate also induced killing [22]. In contrast to prior studies with PHA [20, 21], stimulation with antigens from E. histolytica was found to augment binding intensity of T cells to the trophozoites rather than the binding frequency [22].…”

Section: Direct Killing Of Parasites By Ctlmentioning

confidence: 99%

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Direct Microbicidal Activity of Cytotoxic T-Lymphocytes

Oykhman

Mody

2010

Journal of Biomedicine and Biotechnology

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Cytotoxic T-lymphocytes (CTL) are famous for their ability to kill tumor, allogeneic and virus-infected cells. However, an emerging literature has now demonstrated that CTL also possess the ability to directly recognize and kill bacteria, parasites, and fungi. Here, we review past and recent findings demonstrating the direct microbicidal activity of both CD4+ and CD8+ CTL against various microbial pathogens. Further, this review will outline what is known regarding the mechanisms of direct killing and their underlying signalling pathways.

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Section: Direct Killing Of Parasites By Ctlmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Direct Killing Of Parasites By Ctlmentioning

confidence: 99%

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Direct Microbicidal Activity of Cytotoxic T-Lymphocytes

Oykhman

Mody

2010

Journal of Biomedicine and Biotechnology

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“…Nonetheless, monocytes and macrophages are present in amebic lesions and might play a role both in the destruction of host tissue and also in the killing of trophozo- ites. As MCP-1 is also able to activate cytotoxic T cells (7) and these cells have been found to kill ameba trophozoites (13), this observation is of great importance to pathogenesis. NF-B is an important transcription factor that is usually activated by a classical pathway involving IB degradation and increased NF-B nuclear translocation or a noncanonical pathway involving p65 phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Induction of Monocyte Chemotactic Protein 1 in Colonic Epithelial Cells by Entamoeba histolytica Is Mediated via the Phosphatidylinositol 3-Kinase/p65 Pathway

2007

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The role intestinal epithelial cells play in the pathogenesis of amebic colitis is poorly understood. Herein, we demonstrate that secreted and soluble ameba (Entamoeba histolytica) proteins (SAP) induce expression of the chemoattractant monocyte chemotactic protein (MCP) in the colonic epithelial cell lines Caco-2, T84, and LS174T. MCP-1 mRNA induction was both dose and time dependent, with peak induction occurring at 8 h and with 100 g/ml of SAP. Significant increase in MCP-1 protein expression was observed after 12 h. SAP failed to activate any of the mitogen-activated protein kinase pathways or IB kinase activity. Moreover, inhibiting the classical pathway of NF-B activation did not affect SAP-induced MCP-1 expression. Instead, we find that SAP-induced MCP-1 expression is dependent on posttranslational modification of the NFB p65 subunit. SAP induced phosphorylation of p65 and enhanced NF-B transcriptional activity, which are phosphatidylinositol 3-kinase (PI3 kinase) dependent. Treatment with PI3 kinase inhibitor LY290004 significantly abrogated the activation of Akt, p65, and MCP-1 mRNA induction. We conclude that colonic epithelial cells play a role in the initiation of inflammation by secreting chemokines in response to soluble ameba components.Entamoeba histolytica is an enteric protozoan parasite that is responsible for the disease amebiasis in humans. The disease affects 50 million people globally and is the fourth leading parasitic cause of death (14). Host inflammatory responses are thought to play an important role in the pathogenesis of intestinal amebiasis. However, the roles of intestinal epithelial cells (IEC) and mediators of colonic inflammation have not been fully elucidated.Invasive amebiasis is characterized by infiltration of immune cells such as leukocytes and lymphocytes (5). It has not been well established if this cellular infiltration is a cause or consequence of inflammation. The parasite has previously been shown to elicit interleukin-8 (IL-8) production from colonic epithelial cells (4, 15). IL-8 is a potent chemoattractant primarily for neutrophils, and its secretion alone does not explain the homing of other immune cells such as monocytes and lymphocytes seen in the amebic lesions (5). Monocyte chemotactic protein 1 (MCP-1) belongs to a group of C-C or ␤-chemokines, is produced by a variety of cells, including IEC, and is potently chemotactic for monocytes, lymphocytes, and basophils (10). Recently, amebic infection in a human intestinal xenograft model has been shown to increase a number of genes in the epithelial cells, including the MCP-1 gene (16). However, the mechanism of induction is not known and also it is not clear if ameba components themselves can directly induce this chemokine.The transcription factor NF-B regulates a number of genes involved in immune response and inflammation. It is composed of two subunits, most commonly of p65 and P50. Only p65 has the transactivating domains and hence is critical for NF-B activity. NF-B is activated by different pathways, includ...

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“…Aunque las alteraciones en la función de los linfocitos están menos caracterizadas, tienen un papel importante en la estimulación de macrófagos y activación de células T, muestran actividad amebicida directa y producen interleuquina 2 (IL-2), INF ‫ﻻ‬ y factor de necrosis tumoral beta (FNT β) (respuesta Th1) necesarios para una inmunidad efectiva contra la ameba. Estudios de Salata reportan muerte en el 92 % de trofozoitos por células T CD8+, que requiere un mecanismo de adherencia secuencial y posterior citolisis, estos mecanismos amebicidas de los linfocitos continúan en estudio (47). Así, la activación antígeno-específica de células T, la producción de citoquinas y la actividad efectora de estas células son un componente importante de la inmunidad contra E. histolytica.…”

Section: Inmunidad Celularunclassified