Abstract
Giardia duodenalis, also known as G. intestinalis or G. lamblia, is the major cause of giardiasis leading to diarrheal disease with 280 million people infections annually worldwide. Extracellular vesicles (EVs) have emerged as a ubiquitous mechanism participating in cells communications. The aim of this study is to explore the roles of G. duodenalis EVs (GEVs) in host-pathogen interactions using primary mouse peritoneal macrophages as a model. Multiple methods of electron microscopy, nanoparticle tracking analysis, proteomic assays, flow cytometry, immunofluorescence, qPCR, western blot, ELISA, inhibition assays, were used to characterize GEVs, and explore its effects on the host cell innate immunity as well as the underlying mechanism using primary mouse peritoneal macrophages. Results showed that GEVs displayed typical cup-shaped structure with 150 nm in diameter. GEVs could be captured by macrophages and triggered immune response by increasing the production of inflammatory cytokines Il1β, Il6, Il10, Il12, Il17, Ifng, Tnf, Il18, Ccl20 and Cxcl2. Furthermore, activation of TLR2 and NLRP3 inflammasome signaling pathways involved in this process. In addition, CA-074 methyl ester (an inhibitor of cathepsin B) or zVAD-fmk (an inhibitor of pan-caspase) pretreatment entirely diminished these effects triggered by GEVs exposure. Taken together, these findings demonstrated that GEVs could be internalized into mouse peritoneal macrophages and regulate host cell innate immunity via TLR2 and NLRP3 inflammasome signaling pathways.
Highlights
Giardia duodenalis, known as G. intestinalis or G. lamblia, assemblages A and B are important zoonotic protozoans leading to diarrheal disease especially for children under five years old in developing countries [1]
These findings demonstrated that G. duodenalis EVs (GEVs) could be internalized into mouse peritoneal macrophages and regulate host cell innate immunity via TLR2 and NLRP3 inflammasome signaling pathways
This study demonstrated that GEVs could be internalized into primary mouse peritoneal macrophages, regulate host cell innate immunity via TLR2 and NLRP3 inflammasome signaling pathways, and may provide new targets against giardiasis
Summary
Known as G. intestinalis or G. lamblia, assemblages A and B are important zoonotic protozoans leading to diarrheal disease especially for children under five years old in developing countries [1]. Giardiasis is endemic worldwide and often occurs in groups of travelers [5]. It is estimated that about 280 million diarrhea infections are caused by giardiasis annually [4]. Considering the huge influence brought by G. duodenalis, giardiasis has been added into the Neglected Diseases Initiative by the World Health Organization since 2006 [6,7]. Giardiasis are attracting substantial attention by public. To control and treat with giardiasis, nitazoxanide, metronidazole, and tinidazole are durgs of choice [8,9]. The increasing resistance to these anti-giardiasis drugs are common in recently years [10,11]. It is urgently needed to look for new targets to prevent and treat with giardiasis
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