Javier Sotillo

Javier Sotillo
James Cook University · Australian Institute of Tropical Health and Medicine

35.59
 · 
PhD

About

113
Publications
9,298
Reads
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1,421
Citations
Research Experience
March 2012 - present
James Cook University
Position
  • Postdoctoral Research Fellow
January 2007 - December 2012
University of Valencia
Position

Publications

Publications (113)
Article
Full-text available
Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Her...
Article
Full-text available
Helminth parasites have a remarkable ability to persist within their mammalian hosts, which is largely due to their secretion of molecules with immunomodulatory properties. Although the soluble components of helminth secretions have been extensively studied, the discovery that helminths release extracellular vesicles (EVs) has added further complex...
Preprint
Full-text available
Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host-parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Her...
Article
The ability of the parasitic blood fluke Schistosoma mansoni and other parasitic helminths to manipulate host biology is well recognised, but the mechanisms that underpin these phenomena are not well understood. An emerging paradigm is that helminths transfer their biological cargo to host cells by secretion of extracellular vesicles (EVs). Herein,...
Chapter
The tegument (outer surface) of Schistosoma mansoni and other trematodes is in intimate contact with the host and plays an important role in host-parasite interactions. It is a complex structure that contains hundreds of proteins implicated in a variety of functions, although, so far, only a few proteins have been well characterized. Indeed, a few...
Article
Full-text available
The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a...
Article
Full-text available
Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary...
Article
Full-text available
Hookworms cause a major neglected tropical disease, occurring after larvae penetrate the host skin. Neutrophils are phagocytes that kill large pathogens by releasing neutrophil extracellular traps (NETs), but whether they target hookworms during skin infection is unknown. Using a murine hookworm, Nippostrongylus brasiliensis, we observed neutrophil...
Article
Helminth parasites secrete extracellular vesicles (EVs) into their environment that have potential roles in host-parasite communication, and thus represent potentially useful targets for novel control strategies. Here, we carried out a comprehensive proteomic analysis of two different populations of EVs - 15k pellet and 120k pellet EVs - from Schis...
Article
Opisthorchiasis is a serious public health problem in East Asia and Europe. The pathology involves hepatobiliary abnormalities such as cholangitis, choledocholithiasis and tissue fibrosis that can develop into cholangiocarcinoma. Prevention of infection is difficult as multiple social and behavioral factors are involved, thus, progress on a prophyl...
Conference Paper
Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where t...
Article
Full-text available
Cholinesterase (ChE) function in schistosomes is essential for orchestration of parasite neurotransmission but has been poorly defined with respect to the molecules responsible. Interrogation of the S. mansoni genome has revealed the presence of three ChE domain-containing genes (Smche)s, which we have shown to encode two functional acetylcholinest...
Article
Opisthorchiasis affects millions of people in Southeast Asia and has been strongly associated with bile duct cancer. Current strategic control approaches such as chemotherapy and health education are not sustainable, and a prophylactic vaccine would be a major advance in the prevention of the disease. Tetraspanins are transmembrane proteins previou...
Article
This article reviews the past and present scientific reports regarding Bithynia spp. focusing on the biology, ecology and life cycle of Bithynia snails and their responses to Opisthorchis viverrini infection. Moreover, new data regarding comparative molecular genomics and proteomic approaches have recently revealed novel molecular components involv...
Preprint
Full-text available
Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with fish-borne liver flukes is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor, termed liver fluke granulin (Ov-GRN-1), a homologue of the human progranulin (huPGRN). Secreted Ov-G...
Chapter
Trematode infections are among the most neglected tropical diseases despite their worldwide distribution and extraordinary ability to parasitise many different host species and host tissues. Furthermore, these parasites are of great socioeconomic, medical, veterinary and agricultural importance. During the last 10 years, there have been increasing...
Article
Full-text available
Background: The liver fluke Opisthorchis viverrini infects several million people in Southeast Asia. Adult flukes live in the bile ducts of humans, where they cause hepatobiliary pathology, including cholangiocarcinoma. Here, we investigated the potential of extracellular vesicles (EVs) secreted by the fluke and defined recombinant proteins derive...
Article
Full-text available
Background: Schistosomiasis is a neglected disease affecting hundreds of millions worldwide. Of the three main species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. S. haematobium infection can cause different urogential clinical complications, particularly in the bladder, and...
Preprint
Full-text available
Cholinesterase (ChE) function in schistosomes is essential for orchestration of parasite neurotransmission but has been poorly defined with respect to the molecules responsible. Interrogation of the S. mansoni genome has revealed the presence of three ChE domain containing genes (Smche)s, which we have shown to encode two functional acetylcholinest...
Preprint
Full-text available
The Bithynia snails of B. funiculata, B. siamensis siamensis and B. siamensis goniomphalos, are first intermediate hosts of Opisthorchis viverrini. The success of parasitic infection in snails is related to the host species and efficiency of their internal defense system. Parasitic infections in snails exhibited significant variations in the number...
Article
Full-text available
Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed liver fluke granulin (Ov-grn-1) in pre-malignant lesio...
Preprint
Full-text available
Background: Schistosomiasis is a neglected disease affecting hundreds of millions worldwide. Of the three main species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. S. haematobium infection can cause different urogential clinical complications, particularly in the bladder, and...
Article
Full-text available
Opisthorchis viverrini resides in bile ducts and could be targeted optimally by vaccination, which induces both mucosal and systemic antibodies, reflecting the migratory path of this liver fluke. Tetraspanins are transmembrane proteins essential for tegument formation of O. viverrini and are efficacious as vaccine antigens for diseases caused by th...
Article
Granulins are a family of growth factors involved in cell proliferation. The liver-fluke granulin, Ov-GRN-1, isolated from a carcinogenic liver fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug l...
Preprint
Full-text available
The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a...
Preprint
Full-text available
Infections with several flatworm parasites represent group 1 biological carcinogens, i.e. definite causes of cancer. Infection with the food-borne liver fluke Opisthorchis viverrini causes cholangiocarcinoma (CCA). Whereas the causative agent for most cancers, including CCA in the West, remains obscure, the principal risk factor for CCA in Thailand...
Poster
Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. The importance of excretory/secretory (ES) products in governing host–parasite interacti...
Article
Full-text available
Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm to their hosts, allowing them to establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, hookworms are such potent suppressors of inflammation that they have been used in clinical trials to treat inflammatory bowe...
Data
Prediction of Nippostrongylus brasiliensis extracellular vesicle (EV) miRNA target interactions to murine host genes. Functional map of N. brasiliensis EV miRNAs and their target murine host genes categorized by PantherDB signaling, metabolic, disease, and other pathways. Heat map corresponds to individual targeted genes in the murine host.
Data
Proteomic analysis of extracellular vesicles (EVs) secreted by Nippostrongylus brasiliensis. Details of the identification of the proteins present in the EVs secreted by N. brasiliensis using X!Tandem, Tide, MS-GF+ and OMSSA. All proteins are shown, including contaminants.
Data
Structural (all-vs-all blast) and functional (Blast2GO) comparison of Nippostrongylus brasiliensis- and Trichuris muris-EV proteomes.
Data
Representative images of mouse colons from all the groups examined in the experimental colitis model.
Data
Alluvial diagram depicting interactions between nematode EV miRNAs and mouse host cytokine gene targets. Nippostrongylus brasiliensis (Nb)-EV miRNAs (green), Trichuris muris (Tm)-EV miRNAs (pink), and shared homologs (orange) are presented. Links are colored according to canonical pro- (red) and anti-inflammatory (blue) responses.
Data
Pathway analysis and parsing of Nippostrongylus brasiliensis EV miRNAs and their target murine host genes categorized by PantherDB pathways.
Data
Effects of Trichuris muris secreted fractions in experimental colitis. Mice received a single intraperitoneal injection of 20 µg protein in PBS 1 day prior to intrarectal administration of 2.5 mg of TNBS in 50% ethanol. Data display daily recorded body weight, final clinical examination, colon length, and colon pathology after euthanasia.
Data
Data description on predicted Nippostrongylus brasiliensis miRNA–host target interactions. Table showing the 52 miRNAs identified in the N. brasiliensis extracellular vesicles and their 3′UTR predicted binding sites in the mouse genome.
Article
Full-text available
Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, broadly employed to study the host-dependent mechanisms that govern the evolution of intestinal helminth infections. Resistance against E. caproni homologous secondary infections has been reported in mice and appears to be related to the generation of a local Th2 response...
Article
Introduction: Helminths are multicellular parasites affecting nearly three billion people worldwide. To orchestrate a parasitic existence, helminths secrete different molecules, either in soluble form or contained within extracellular vesicles (EVs). EVs are secreted by most cell types and organisms, and have varied roles in intercellular communica...
Article
Full-text available
Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where t...
Chapter
The omics technologies have improved our understanding of the molecular events that underpin host–parasite interactions and the pathogenesis of parasitic diseases. In the last decade, proteomics and genomics in particular have been used to characterize the surface and secreted products of the carcinogenic liver fluke Opisthorchis viverrini and reve...
Article
Full-text available
There is a rapidly growing body of evidence that production of extracellular vesicles (EVs) is a universal feature of cellular life. More recently, EVs have been identified in a broad range of both unicellular and multicellular parasites where they play roles in parasite–parasite intercommunication as well as parasite–host interactions. Parasitic h...
Poster
Parasitic helminth infections in livestock are responsible for significant economic losses particularly in developing and tropical regions of the world. Soil-transmitted helminths affect more than 1.5 billion people causing great socio-economic impact. Among these, hookworms, roundworms and whipworms are of particular importance due to their high e...
Conference Paper
Full-text available
Parasitic helminth infections in livestock are responsible for significant economic losses particularly in developing and tropical regions of the world. Soil-transmitted helminths affect more than 1.5 billion people causing great socio-economic impact. Among these, hookworms, roundworms and whipworms are of particular importance due to their high e...
Article
The current strategy for the control of helminth infections relies on chemotherapy. However, resistance appearance is promoting the necessity of developing new drugs against trematodes. Herein, potential trematocidal effects of garlic (Allium sativum) are investigated in the context of intestinal foodborne trematodes, employing the Echinostoma capr...
Article
Granulins are a family of protein growth factors that are involved in cell proliferation. An orthologue of granulin from the human parasitic liver fluke Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates wound repair. Recombinant Ov-GRN-1 production is complex, and poses an obstacle for clinical development. To identify...
Article
Full-text available
Different reports have highlighted the potential use of helminths and their secretions in the treatment of inflammatory bowel disease (IBD) conditions; however, no reports have investigated their effects at a proteome level. Herein, we characterise the protein expression changes that occur in lamina propria (LP) and the intestinal epithelial cells...
Article
Full-text available
Bithynia siamensis goniomphalos is a freshwater snail that serves as the first intermediate host of the human liver fluke Opisthorchis viverrini. This parasite is a major public health problem in different countries throughout the Greater Mekong sub-region (Thailand, southern Vietnam, Lao PDR and Cambodia). Chronic O. viverrini infection also resul...
Article
\textit{Bithynia siamensis goniomphalos}$ is a freshwater snail that serves as the first intermediate host of the human liver fluke $\textit{Opisthorchis viverrini}$. This parasite is a major public health problem in different countries throughout the Greater Mekong sub-region (Thailand, southern Vietnam, Lao PDR and Cambodia). Chronic $\textit{O....
Article
Full-text available
Echinostoma caproni is an intestinal trematode that has been extensively used as an experimental model to investigate the factors determining the resistance to intestinal helminths or the development of chronic infections. ICR mice are permissive hosts for E. caproni in which chronic infections are developed, concomitantly with local Th1 responses,...
Article
Full-text available
Background Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasi...
Article
Full-text available
Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, li...
Article
Full-text available
Significance: Intestinal helminthiases are highly prevalent parasitic infections with about 1 billion people infected worldwide. In this scenario, better understanding of host-parasite relationships is needed to elucidate the factors that determine intestinal helminth rejection. The intestinal trematode Echinostoma caproni has been broadly employe...
Article
The association between liver fluke infection caused by Opisthorchis viverrini and cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium) has been well established. Multiple mechanisms play a role in the development of CCA, but the excretory/secretory products released by O. viverrini (OvES) represent the major interface between the...
Article
Enhanced mucus production and release appears to be a common mechanism for the clearance of intestinal helminths and this expulsion is normally mediated by Th2-type immune responses. In order to investigate the factors determining the expulsion of intestinal helminths, we have analyzed in vivo expression of mucin genes at the site of infection in t...
Article
Full-text available
Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini sec...
Article
Full-text available
Herein we show for the first time that S. mansoni adult worms secrete exosome-like extracellular vesicles (EVs) ranging from 50-130 nm in size. EVs were collected from the excretory/secretory products of cultured adult flukes and purified by Optiprep density gradient, resulting in highly pure EV preparations as confirmed by transmission electron mi...
Article
Full-text available
Background: Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode that has been extensively used as experimental model to investigate the factors determining the expulsion of intestinal helminths or, in contrast, the development of chronic infections. Herein, we analyze the changes in protein expression induced by E. caproni...
Article
Full-text available
The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD...