Giardia duodenalis Cathepsin B Proteases Degrade Intestinal Epithelial Interleukin-8 and Attenuate Interleukin-8-Induced Neutrophil Chemotaxis

Cotton, James A.; Bhargava, Amol; Ferraz, Jose G.; Yates, Robin M.; Beck, Paul L.; Buret, André G.

doi:10.1128/iai.01771-14

Cited by 85 publications

(94 citation statements)

References 98 publications

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“…230 In contrast, Giardia duodenalis cathepsin B cysteine proteases were shown to degrade CXCL8 and attenuate CXCL8-induced PMN chemotaxis. 231 This research may explain how in vivo G. duodenalis infections were capable of attenuating granulocyte infiltration induced by intrarectal instillation of C. difficile TcdA/TcdB or reducing CXCL chemokine expression from ex vivo inflamed intestinal mucosal biopsy tissues. 232 It remains unknown whether other GI pathogens produce proteases or factors capable of modifying CXCL8 and whether this could, potentially, affect the pathogenesis of infection.…”

Section: Degranulationmentioning

confidence: 94%

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences

Cotton¹,

Platnich²,

Muruve³

et al. 2016

IJICMR

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Section: Degranulationmentioning

confidence: 94%

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences

Cotton¹,

Platnich²,

Muruve³

et al. 2016

IJICMR

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“…The same group also found that giardiasis may enhance the outcome of atopic dermatitis allergic reactions in school children [84]. But G. duodenalis infection was also found to reduce granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue suggesting modulating immune responses during giardiasis [85].…”

Section: Adaptive Immune Responsesmentioning

confidence: 94%

“…Th2 responses have been associated with a broad variety of initiating mechanisms including protease activity, metabolic stresses induced by the pathogen or by pathogen tissue damage [73]. In this respect, it is noteworthy that G. duodenalis parasites secrete a broad variety of cysteine proteases [85,45,114,115] that may also play a part in a PRR-independent immune response. Such proteins were shown to stimulate a mixed Th1/Th2-like in mice [116].…”

Section: Giardia Factors Known To Interact With the Immune Systemmentioning

confidence: 99%

The Immunological Enigma of Human Giardiasis

Klotz

Aebischer

2015

Curr Trop Med Rep

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Giardiasis is a major cause of enteritis in humans worldwide. The disease is caused by two very distinct genetic groups (referred to as assemblages A and B) of the species complex Giardia duodenalis. The trophozoites stage colonizes the duodenum and jejunum of the small intestine and may cause a broad variety of disease outcomes that reach from asymptomatic carriers to patients with acute or chronic severe gastrointestinal complaints. Studies in immunocompromised patients imply that antibody-mediated acquired immune responses and a minimal T cell availability are of major importance for parasite clearance. These mechanisms likely play in concert with natural resistance mechanisms that are present in the intestinal mucosa. In humans no sterile immunity is acquired after infection. Epidemiological studies further suggest passive protection from symptomatic giardiasis in breastfed children. However, there is a fundamental lack of knowledge about the underlying immunological mechanisms of human giardiasis.

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“…The G. duodenalis genome contains genes for at least 23 cathepsin cysteine proteases, the majority of which have no described function [94,95]. However, several G. duodenalis cathepsin proteases are upregulated upon exposure to intestinal epithelial cells [87,96]. Even though cathepsin protease assays suggested that assemblage B G. duodenalis trophozoites secrete cysteine proteases with similar activity, these failed to degrade CXCL8, indicative of an isolate-specific effect [28•, 87].…”

Section: Immuno-modulation By Giardia and Symptom Variabilitymentioning

confidence: 99%

Giardia duodenalis: New Research Developments in Pathophysiology, Pathogenesis, and Virulence Factors

et al. 2015

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Giardia duodenalis is a very common, ubiquitous, intestinal protozoan parasite infecting animals and humans. Of the eight distinct genetic assemblages known to date, assemblages A and B are infectious to humans. Giardia is the most commonly recognized cause of traveller's diarrhea. Giardiasis impairs weight gain and is responsible for a variety of extraintestinal and post-infectious complications, including postinfectious irritable bowel syndrome, chronic fatigue, failure to thrive, and cognitive impairment. Giardiasis occurs in the absence of invasion of the intestinal tissues by the trophozoites and in the absence of any overt inflammatory cell infiltration, with the exception of a modest increase in intraepithelial lymphocytes and mast cells. In endemic parts of the World where the infection is often concurrent with bacterial enteritis causing inflammation-driven diarrheal disease, giardiasis appears to be protective against diarrhea. Recent observations have demonstrated that this effect may be due to a direct immuno-modulating effect of the parasite via its cathepsin B cysteine protease which cleaves pro-inflammatory CXCL8. No known toxin has yet been directly implicated in the pathophysiology of giardiasis. Diarrhea in giardiasis is mostly malabsorptive in nature, rather than hypersecretory. Findings from ongoing research indicate that the post-infectious effects of giardiasis may be due to microbiota dysbiosis induced by the parasite during the acute phase of infection.

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Giardia duodenalis Cathepsin B Proteases Degrade Intestinal Epithelial Interleukin-8 and Attenuate Interleukin-8-Induced Neutrophil Chemotaxis

Cited by 85 publications

References 98 publications

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences

The Immunological Enigma of Human Giardiasis

Giardia duodenalis: New Research Developments in Pathophysiology, Pathogenesis, and Virulence Factors

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