Entamoeba histolytica cysteine protease 2 (EhCP2) modulates leucocyte migration by proteolytic cleavage of chemokines

Abstract

Human amoebiasis is a disease produced by infection with the protozoan Entamoeba histolytica currently affecting many millions of people worldwide. Amoebic colitis is the most common clinical manifestation. Host protective immunity involves participation of both humoral and cellular responses. However, the mechanisms involved in immune evasion are not clear and remain under investigation. One of these mechanisms could be associated with the ability of parasite proteases to modulate or interfere with the inflammation process, which is initiated by expression of pro-inflammatory cytokines such as chemokines. To further clarify the potential role of cysteine proteases in modulating chemokine-mediated functions, we have analysed the ability of Entamoeba histolytica cysteine protease 2 (EhCP2) to have an effect on the chemotaxis of leucocytes by chemokine cleavage. We find that EhCP2 is capable of cleaving chemokines CCL2, CCL13 and CXCL8, and the resulting proteolysis products modulate the chemotaxis of leucocytes when compared to that induced by intact chemokine. Thus, the extracellular activity of the cysteine proteases affects chemokine-mediated responses and could be considered as part of the mechanisms used by Entamoeba histolytica to circumvent the host immune responses.

Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion

“…CPB could contribute to the impaired secretion of chemokines and cytokines observed in response to L . mexicana and/or released CPB could modulate local cell recruitment through potential impact on chemokines, an effect previously reported by other protozoan CPBs [ 38 , 39 ]. Neutrophils with their numerous cytosolic proteases may contribute to CPB activity and favor chemokine inhibition, an area that remains to be investigated.…”

Preliminary molecular characterization of the human pathogen Angiostrongylus cantonensis

“…The infectious third-stage larvae of A. cantonensis usually secrete proteolytic enzymes after infecting the host. The functions served by different protease families include degradation of host hemoglobin [ 35 - 37 ], larval penetration and migration [ 38 - 40 ], and immune evasion [ 41 - 45 ]. Of the 90 functional terms identified under the category of "catalytic activity", more than 10% are proteases, including serine, cysteine and aspartic proteases (Table 1 ).…”

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

“…Parasitic cysteine proteases have been shown to prevent activation of proinflammatory transcription factors (88), degrade host effector molecules (89), promote specific host immune responses (90,91), and cleave host chemokines (46,87). Prior to this study, reports had described roles for a G. duodenalis catB protease in trophozoite encystation and excystation (41), but the role of these proteases in disease pathogenesis and host immunity has remained largely speculative (43,92,93).…”

“…However, several G. duodenalis cathepsin proteases are upregulated upon exposure to IECs (43). While some parasites may use cathepsin cysteine proteases to evade or modulate their host's immune responses (reviewed in references 44 and 45), previous research has demonstrated that Entamoeba histolytica cysteine protease 2 (EhCP2) cleaves CXCL8 into a more potent isoform that enhances PMN chemotaxis (46). We hypothesized that Giardia cathepsin cysteine proteases may be involved in modulating acute proinflammatory responses within the intestinal epithelium.…”