Regulation of Toll‐like receptor‐2 expression by the Gal‐lectin of<i>Entamoeba histolytica</i>

Kammanadiminti, Srinivas; Mann, Barbara J.; Dutil, Lisa; Chadee, Kris

doi:10.1096/fj.03-0578fje

Cited by 61 publications

(48 citation statements)

References 47 publications

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“…Very recently, it has also been demonstrated that Gal/GalNAc lectin of E. histolytica was bound and captured by different target cells and that host cells containing the lectin showed signs of cell damage (56). Furthermore, amebic galectin purified from E. histolytica has been shown to stimulate macrophages to induce TNF-␣ production (57) and TLR-2 expression (58). Therefore, for a better understanding of the signaling role of amebic galectin in cell function it will be extremely important to investigate whether the purified or recombinant forms of amebic galectin induce the ROS-mediated signaling events required for neutrophil apoptosis.…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase-Derived Reactive Oxygen Species-Mediated Activation of ERK1/2 Is Required for Apoptosis of Human Neutrophils Induced by Entamoeba histolytica

Sim

Yong

Park

et al. 2005

The Journal of Immunology

116

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The extracellular tissue penetrating protozoan parasite Entamoeba histolytica has been known to induce host cell apoptosis. However, the intracellular signaling mechanism used by the parasite to trigger apoptosis is poorly understood. In this study, we investigated the roles of reactive oxygen species (ROS), and of MAPKs in the Entamoeba-induced apoptosis of human neutrophils. The neutrophils incubated with live trophozoites of E. histolytica revealed a marked increase of receptor shedding of CD16 as well as phosphatidylserine (PS) externalization on the cell surface. The Entamoeba-induced apoptosis was effectively blocked by pretreatment of cells with diphenyleneiodonium chloride (DPI), a flavoprotein inhibitor of NADPH oxidase. A large amount of intracellular ROS was detected after exposure to viable trophozoites, and the treatment with DPI strongly inhibited the Entamoeba-induced ROS generation. However, a mitochondrial inhibitor rotenone did not attenuate the Entamoeba-induced ROS generation and apoptosis. Although E. histolytica strongly induced activation of ERK1/2 and p38 MAPK in neutrophils, the activation of ERK1/2 was closely associated with ROS-mediated apoptosis. Pretreatment of neutrophils with MEK1 inhibitor PD98059, but not p38 MAPK inhibitor SB202190, prevented Entamoeba-induced apoptosis. Moreover, DPI almost completely inhibited Entamoeba-induced phosphorylation of ERK1/2, but not phosphorylation of p38 MAPK. These results strongly suggest that NADPH oxidase-derived ROS-mediated activation of ERK1/2 is required for the Entamoeba-induced neutrophil apoptosis.

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Section: Discussionmentioning

confidence: 99%

NADPH Oxidase-Derived Reactive Oxygen Species-Mediated Activation of ERK1/2 Is Required for Apoptosis of Human Neutrophils Induced by Entamoeba histolytica

Sim

Yong

Park

et al. 2005

The Journal of Immunology

116

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“…Different surface components of trophozoites were shown to be recognized by macrophages via TLR-2 and TLR-4 signaling (31). Upregulated TLR-2 expression was observed in macrophages exposed to Gal/GalNac lectin of E. histolytica, resulting in NF-κB activation and proinflammatory cytokine production (32). Macrophages lacking TLR-2 and TLR-4 showed impaired response to E. histolytica lipopeptidophosphoglycan (LPPG), suggesting an essential role of pattern recognition for the macrophage response (31).…”

Section: Innate Cell-mediated Immunity To E Histolyticamentioning

confidence: 99%

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

Guo

Houpt

Petri

2007

Current Opinion in Immunology

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The host-parasite relationship is based on a series of interplays between host defense mechanisms and parasite survival strategies. Progress has been made in understanding the role of host immune response in amebiasis. While host cells elaborate diverse mechanisms for pathogen expulsion, amebae have also developed complex strategies to modulate host immune response and facilitate their own survival. This paper will give an overview of current research on the mutual interactions between host and Entamoeba histolytica in human and experimental amebiasis. Understanding this crosstalk is crucial for the effective design and implementation of new vaccines and drugs for this leading parasitic disease.

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“…Although TLRs are able to recognize a broad spectrum of structurally diverse ligands ranging from small molecules and polynucleotides to lipopeptides from synthetic, host and pathogen sources, there is surprisingly little literature on the direct interaction of TLRs with lectins [6,7]. For example, TLR4 has been shown to respond to a growing catalogue of structurally diverse ligands ranging from the seminal ligand, LPS to taxol [8] and hyaluronan [9].…”

Section: Introductionmentioning

confidence: 99%

Plant lectins are novel Toll-like receptor agonists

Unitt

Hornigold

2011

Biochemical Pharmacology

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The T cell mitogen and plant glycoprotein, phytohaemagglutinin (PHA), is commonly used to stimulate peripheral blood mononuclear cell (PBMC) preparations to produce IL-2, IL-5, GM-CSF and IFN- and so provide an assay to detect immunosuppressants like FK506 and anti-inflammatories such as PDE IV inhibitors.During the early discovery of novel TLR agonists for the treatment of asthma we initially showed that PHA-L is a specific human TLR4 agonist, devoid of effects on equivalent TLR4 null cells. This TLR4 agonism was not due to LPS contamination of PHA-L, as polymyxin B was ineffective and unlike PHA-L, LPS did not stimulate TLR5 or TLR2/6. Also this specific PHA-L agonism of TLR4 was shown for different PHA forms, for example, PHA-P.This TLR lectin pharmacology finding was further explored by testing a broader panel of plant lectin representatives for agonism against a suite of hrTLR cell reporter assays (2/6, 3, 4, 5, 7, 8 and 9). Soyabean agglutinin (SBA), concanavalin A (ConA) and PHA lectin family members only stimulated extracellular TLRs (2/6, 4 and 5) probably due to lack of intracellular access, whilst other lectins were either pan-active (WGA) or inactive (AIL).Interestingly SBA only stimulated TLR4, ConA, TLR2/6 and PHA-L, TLR2/6, 4 and 5.As each lectin family exhibits different sugar ligand specificity for interaction, these results suggest that the pharmacology of this TLR agonism is encoded by the lectin's carbohydrate recognition motifs and the appropriate surface presentation of these motifs on different TLRs.

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Regulation of Toll‐like receptor‐2 expression by the Gal‐lectin ofEntamoeba histolytica

Cited by 61 publications

References 47 publications

NADPH Oxidase-Derived Reactive Oxygen Species-Mediated Activation of ERK1/2 Is Required for Apoptosis of Human Neutrophils Induced by Entamoeba histolytica

NADPH Oxidase-Derived Reactive Oxygen Species-Mediated Activation of ERK1/2 Is Required for Apoptosis of Human Neutrophils Induced by Entamoeba histolytica

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

Plant lectins are novel Toll-like receptor agonists

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