Hepatocyte nuclear factor 4 located in different developmental stages in Schistosoma japonicum and involved in important metabolic pathways.

BACKGROUND: Nuclear receptors (NRs) are vital for regulating gene expression un organisms. Hepatocyte nuclear factor 4 (HNF4), a class of NRs, participates in blood feeding and intestinal maintenance in schistosomes. However, there is limited research on the molecular and functional characterization of HNF4 in Schistosoma japonicum (S. japonicum). METHODS: Highly specific polyclonal antibodies were generated to analyze the expression and tissue localization of S. japonicum HNF4 (SjHNF4). The potential biological functions of SjHNF4 were characterized by transcriptome and pull-down analysis. Subsequently, enrichment analysis was performed to identify the specific signaling pathways linked to SjHNF4. RESULTS: The SjHNF4 protein was expressed heterologously and purified successfully. High purity and high potency polyclonal antibodies were further prepared. The expression of SjHNF4 was higher in female compared to male worms at both transcriptional and protein levels. Female worms expressed SjHNF4 in their perithecium, reproductive system, and certain parts of the intestinal tissues. SjHNF4 was also detected in the perithecium of male worms, as well as in the head, body of cercaria, and eggs. Furthermore, our findings highlighted the potential role of SjHNF4 in blood feeding and its interaction with crucial pathways such as glucose metabolism, lipid metabolism, and nucleotide metabolism. CONCLUSIONS: This study shed light on the location of SjHNF4 in different life stages of S. japonicum, particularly associated with the female schistosomes. A strong correlation was observed between SjHNF4 and essential metabolic pathways. These findings laid a solid groundwork for the research on the relationship between NRs and schistosomes.

Metagenomic analysis of the intestinal microbiome reveals the potential mechanism involved in Bacillus amyloliquefaciens in treating schistosomiasis japonica in mice.

Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as dysbiosis of intestinal microbiome. Previously, the probiotic Bacillus amyloliquefaciens has been shown to alleviate the pathological injuries in mice infected with Schistosoma japonicum by improving the disturbance of the intestinal microbiota. However, the underlying mechanisms involved in this process remain unclear. In this study, metagenomics sequencing and functional analysis were employed to investigate the differential changes in taxonomic composition and functional genes of the intestinal microbiome in S. japonicum-infected mice treated with B. amyloliquefaciens. The results revealed that intervention with B. amyloliquefaciens altered the taxonomic composition of the intestinal microbiota at the species level in infected mice and significantly increased the abundance of beneficial bacteria. Moreover, the abundance of predicted genes in the intestinal microbiome was also significantly changed, and the abundance of xfp/xpk and genes translated to urease was significantly restored. Further analysis showed that Limosilactobacillus reuteri was positively correlated with several KEGG Orthology (KO) genes and metabolic reactions, which might play important roles in alleviating the pathological symptoms caused by S. japonicum infection, indicating that it has the potential to function as another effective therapeutic agent for schistosomiasis. These data suggested that treatment of murine schistosomiasis japonica by B. amyloliquefaciens might be induced by alterations in the taxonomic composition and functional gene of the intestinal microbiome in mice. We hope this study will provide adjuvant strategies and methods for the early prevention and treatment of schistosomiasis japonica. IMPORTANCE: Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with Schistosoma japonicum and significant increase in the abundance of beneficial bacteria after the intervention of Bacillus amyloliquefaciens. At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and xfp/xpk related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of Limosilactobacillus reuteri in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.

Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. METHODS: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. RESULTS: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. CONCLUSION: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis.

Bacillus amyloliquefaciens alleviates the pathological injuries in mice infected with Schistosoma japonicum by modulating intestinal microbiome.

Schistosoma japonicum causes serious pathological organ damage and alteration of the intestinal microbiome in the mammalian host, threatening the health of millions of people in China. Bacillus amyloliquefaciens has been reported to be able to alleviate the damage to the gut and liver and maintain the homeostasis of the intestinal microenvironment. However, it was unclear whether B. amyloliquefaciens could alleviate the hepatic and intestinal symptoms caused by S. japonicum. In this study, the intragastric administration of B. amyloliquefaciens was performed to treat S. japonicum-infected mice during the acute phase. Histopathological analysis and 16S rRNA gene sequencing were used to evaluate the pathological damage and changes in the intestinal microbiome. The results of the study showed that B. amyloliquefaciens treatment significantly reduced the degree of granuloma and fibrosis in infected mice. Additionally, recovery of diversity in the intestinal microbiome, decrease in the relative abundance of potential pathogenic bacteria such as Escherichia-Shigella, and reshaping of the interactive network between genera in the intestine were also observed after treatment with B. amyloliquefaciens. Our findings indicated that treatment with B. amyloliquefaciens effectively alleviated the pathological injuries of the liver and intestine in mice infected with S. japonicum by modulating the intestinal microbiome, implying that this probiotic can function as an effective therapeutic agent against schistosomiasis. We hope our study will provide auxiliary strategies and methods for the early prevention of schistosomiasis japonica.

Exorchis sp. in the catfish Silurus asotus and Oncomelania hupensis in marshlands of Poyang Lake, China: A potential biological control tool for Schistosoma japonicum.

Oncomelania hupensis is the obligate intermediate host of Schistosoma japonicum, highlighting the medical importance of interrupting this unique and long-standing parasite-host interaction in controlling schistosomiasis transmission. It has been reported that a catfish trematode Exorchis sp. could have the potential to function as an effective anti-schistosomal agent in the snail host. However, the feasibility of this eco-friendly biological control strategy should be comprehensively investigated and evaluated in endemic areas for schistosomiasis. In this study, a field survey was conducted from 2012 to 2016 in the marshlands of Poyang Lake, which is one of the highly endemic regions for schistosomiasis in China. Results showed that more than half of Silurus asotus (65.79%) were infected with Exorchis sp., and the average intensity of infection was 14.21 per fish. And the average infection rate of Exorchis sp. in O. hupensis is 1.11%. These findings indicated that there are abundant biological resources for the implementation of this biology control strategy in the marshlands of Poyang Lake. The data presented here provide solid evidences for the practical application of this biological control strategy, thereby contributing to achieving the goals of the elimination of schistosomiasis.

Pattern recognition receptor signaling and innate immune responses to schistosome infection.

Schistosomiasis remains to be a significant public health problem in tropical and subtropical regions. Despite remarkable progress that has been made in the control of the disease over the past decades, its elimination remains a daunting challenge in many countries. This disease is an inflammatory response-driven, and the positive outcome after infection depends on the regulation of immune responses that efficiently clear worms and allow protective immunity to develop. The innate immune responses play a critical role in host defense against schistosome infection and pathogenesis. Initial pro-inflammatory responses are essential for clearing invading parasites by promoting appropriate cell-mediated and humoral immunity. However, elevated and prolonged inflammatory responses against the eggs trapped in the host tissues contribute to disease progression. A better understanding of the molecular mechanisms of innate immune responses is important for developing effective therapies and vaccines. Here, we update the recent advances in the definitive host innate immune response to schistosome infection, especially highlighting the critical roles of pattern recognition receptors and cytokines. The considerations for further research are also provided.

Structural insights into the redox regulation of Oncomelania hupensis TRP14 and its potential role in the snail host response to parasite invasion.

The freshwater amphibious snail Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum, but little attention has been paid to the interaction between the two. In snails, the production of reactive oxygen species (ROS) by hemocytes has been shown to be vital for snail immune defense against schistosome infection. However, excessive ROS accumulation could lead to oxidative damage, requiring the antioxidant system for maintaining the cellular redox homeostasis. Previously we identified a thioredoxin-related protein of 14 kDa from O. hupensis (OhTRP14), and showed that it was involved in the scavenging of ROS in circulating hemocytes. Here, we confirmed that OhTRP14 plays a potential role in the snail host response to parasite challenge and determined the crystal structures of OhTRP14 in two different states (oxidized and transition state). The overall structure revealed a typical Trx fold and is similar to that of human TRP14 (hTRP14), but there were significant structural differences between the two states. Noticeably, there was a different pair of thiol groups from Cys30 and Cys44 in the transition state of OhTRP14, were with the similar separation of 2.9 Å as that (2.6 Å) between Cys41 and Cys44, but in a different orientation, suggesting that the Cys30 is likely to function as an important molecular switch involved in the oxidoreductase activity of OhTRP14. Comparative studies between OhTRP14 and hTRP14 by analyzing the surface characteristics, charge distribution and oxidoreductase activity toward insulin demonstrated they might have similar substrates. The results are expected to provide structural insights into the redox regulation of OhTRP14 and contribute to better understanding of TRP14 family. DATA DEPOSITION: The atomic coordinates of the structure and the structure factors were deposited in Protein Data Bank with PDB ID codes 7XQ3 and 7XPW.

A case of severe hookworm infection. / 临床极重症钩虫感染1例.

With the improvement of sanitation, the infection rate of hookworm is greatly reduced and the severe infected case is rarely reported. Combined morphological and molecular biological examinations, a severe hookworm infection patient was diagnosed in Department of Laboratorial Examination, Quanzhou First Affiliated Hospital of Fujian Medical University. The morphological methods such as direct fecal smear microscopy, saturated brine flotation and hookworm larvae culture methods were used to identify the eggs and larvae from stool samples of the patient. There were a large number of hookworm eggs in patient's stool samples, and the average count was 60 840 per gram by modified Kato method, which belonged to severe hookworm infection. Meanwhile, to distinguish the hookworm species, the semi-nested RT-PCR assay was employed to detect hookworm internal transcribed spacer series from eggs in patient's stool samples, and the result showed that the hookworm species was confirmed to be Necator americanus.

A secreted MIF homologue from Trichinella spiralis binds to and interacts with host monocytes.

Trichinella spiralis is a very successful parasite capable of surviving in many mammal hosts and residing in muscle tissues for long periods, indicating that it must have some effective strategies to escape from or guard against the host immune attack. The functions of MIF have been studied in other parasites and demonstrated to function as a virulence factor aiding in their survival by modulating the host immune response. However, the functions of Trichinella spiralis MIF (TsMIF) have not been addressed. Here, we successfully obtained the purified recombinant TsMIF and anti-TsMIF serum. Our results showed that TsMIF was expressed in all the Trichinella spiralis developmental stages, especially highly expressed in the muscle larvae (ML) and mainly located in stichocytes, midgut, cuticle, muscle cells of ML and around intrauterine embryos of female adults. We also observed TsMIF could be secreted from ML and bind to host monocytes. Next, our data demonstrated that TsMIF not only stimulated the phosphorylation of ERK1/2 and cell proliferation by binding to the host cell surface receptor CD74, but also interacted with a host intracellular protein, Jab1, which is a coactivator of AP-1 transcription. We concluded the secreted TsMIF plays an important role in the interaction between Trichinella spiralis and its host and could be a potential drug or vaccine target molecule against Trichinella spiralis infection.

Correction: Liu et al. Anti-Toxoplasma gondii Effects of a Novel Spider Peptide XYP1 In Vitro and In Vivo. Biomedicines 2021, 9, 934.

In the original publication, there were mistakes in Figure 3C, Figure 6B and Figure S2A,B as published [...].

Anti-Toxoplasma gondii Effects of a Novel Spider Peptide XYP1 In Vitro and In Vivo.

Toxoplasmosis, caused by an obligate intracellular parasite Toxoplasma gondii, is one of the most prevalent zoonoses worldwide. Treatments for this disease by traditional drugs have shown numerous side effects, thus effective alternative anti-Toxoplasma strategies or drugs are urgently needed. In this study, a novel spider peptide, XYP1, was identified from the cDNA library of the venom gland of the spider Lycosa coelestis. Our results showed that XYP1 has potent anti-Toxoplasma activity in vitro and in vivo. Specifically, treatment with XYP1 significantly inhibited the viability, invasion and proliferation of tachyzoites with low cytotoxicity (IC50 = 38.79 µΜ) on human host cells, and increased the survival rate of mice acutely infected with T. gondii. Next, scanning electron microscopy, transmission electron microscopy and RNA sequencing were employed to further explore the functional mechanism of XYP1, and the results indicated that XYP1 causes membrane perforation, swelling and disruption of tachyzoites, which could be closely associated with differential expression of several membrane-associated proteins including HSP29. In conclusion, XYP1 may be a promising new drug candidate for the treatment of toxoplasmosis.

Protein Kinases: Potential Drug Targets Against Schistosoma japonicum.

Schistosoma japonicum (S. japonicum) infection can induce serious organ damage and cause schistosomiasis japonica which is mainly prevalent in Asia and currently one of the most seriously neglected tropical diseases. Treatment of schistosomiasis largely depends on the drug praziquantel (PZQ). However, PZQ exhibits low killing efficacy on juvenile worms and the potential emergence of its drug resistance is a continual concern. Protein kinases (PKs) are enzymes that catalyze the phosphorylation of proteins and can participate in many signaling pathways in vivo. Recent studies confirmed the essential roles of PKs in the growth and development of S. japonicum, as well as in schistosome-host interactions, and researches have screened drug targets about PKs from S. japonicum (SjPKs), which provide new opportunities of developing new treatments on schistosomiasis. The aim of this review is to present the current progress on SjPKs from classification, different functions and their potential to become drug targets compared with other schistosomes. The efficiency of related protein kinase inhibitors on schistosomes is highlighted. Finally, the current challenges and problems in the study of SjPKs are proposed, which can provide future guidance for developing anti-schistosomiasis drugs and vaccines.

Combined transcriptomics and proteomics to identify differential proteins involved in the immune response to the parasite schistosoma japonicum in snail hosts pre-infected with exorchis sp.

Oncomelania hupensis is the obligate intermediate host of Schistosoma japonicum, and it also serves as the first intermediate host for Exorchis sp., which uses Parasilurus asoyus as its definitive host rather than humans. In previous studies, Tang et al. found that all S. japonicum larvae can be blocked and killed in O. hupensis pre-infected with Exorchis sp. eggs. However, the molecular and cellular mechanisms involved in this process remain unclear. Therefore, in the present study, a combined transcriptomic and proteomic analysis was performed to identify the differential proteins involved in the immune response to the parasite S. japonicum in the O. hupensis snail host pre-infected with Exorchis sp. trematodes. The results showed that a total of 46,162 unigenes were obtained with 23,535 (50.98%) unigenes annotated in relevant databases, and 3811 proteins from O. hupensis were identified. In addition, iTRAQ-based quantitative proteomic analysis demonstrated that among three groups (OhSj-1_vs_OhN-1, OhE-1_vs_OhN-1 and OhES-1_vs_OhN-1), there were 146 common differential proteins including 44 up-regulated proteins and 90 down-regulated proteins, and 195 differential proteins exclusive to only one experimental group, including 91 up-regulated proteins and 104 down-regulated proteins, which were defined as the Common group and the Only group, respectively. KEGG analysis showed that 15 and 11 differential proteins were annotated in "Infectious diseases" in the Common group and the Only group, respectively, indicating that these proteins may be involved in the snail host immune response to parasite infection. These data will be helpful for better understanding the host-parasite interaction, and could pave the way towards exploring the mechanisms involved in the biological control on S. japonicum in O. hupensis. They also provide valuable information about developing new anti-schistosomiasis strategies.

Structural and functional insights into macrophage migration inhibitory factor from Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum. As an irreplaceable prerequisite in the transmission and prevalence of schistosomiasis japonica, an in-depth study of this obligate host-parasite interaction can provide glimpse into the molecular events in the competition between schistosome infectivity and snail immune resistance. In previous studies, we identified a macrophage migration inhibitory factor (MIF) from O. hupensis (OhMIF), and showed that it was involved in the snail host immune response to the parasite S. japonicum. Here, we determined the crystal structure of OhMIF and revealed that there were distinct structural differences between the mammalian and O. hupensis MIFs. Noticeably, there was a projecting and structured C-terminus in OhMIF, which not only regulated the MIF's thermostability but was also critical in the activation of its tautomerase activity. Comparative studies between OhMIF and human MIF (hMIF) by analyzing the tautomerase activity, oxidoreductase activity, thermostability, interaction with the receptor CD74 and activation of the ERK signaling pathway demonstrated the functional differences between hMIF and OhMIF. Our data shed a species-specific light on structural, functional, and immunological characteristics of OhMIF and enrich the knowledge on the MIF family.

Helminth parasites of the Nile Rat, Arvicanthis niloticus, from Shendi area, Sudan

Eighty nine rats, Arvicanthis niloticus, were collected from the horticultural fields of Shendi area in Sudan, between January and June 2018, and examined for the first time for helminth parasites. Thirty seven (41.6%) of the collected rats were infected, with an overall mean intensity of 4.4 helminths per a rat. A total of 6 helminth species were identified including three nematodes (Nippostrongylus brasiliensis, Monanema nilotica and Capillaria hepatica) and three cestodes (Hymenolepis diminuta, H. nana and Taenia taeniae formis). The most prevalent helminth was found to be the nematode, N. brasiliensis (21.3%), followed by the cestode, H. diminuta (10.1%), while the least was the nematode, C. hepatica (1.1%). Higher prevalence and intensity of infection were observed among older rats. Likewise, male rats were found to harbor a higher prevalence and intensity of infection. In conclusion, the rat, A. niloticus in Shendi area has found to be parasitized by various species of helminths, which some are of zoonotic importance, thus, any possible contact between this rat and humans or their pets may pose potential risk to public health.

Identification and functional characterization of thioredoxin-related protein of 14 kDa in Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

Oncomelania hupensis is the unique intermediate host of the blood fluke Schistosoma japonicum, which causes schistosomiasis. In snails, highly toxic reactive oxygen species (ROS) can be continually generated by hemocytes in response to foreign particles or pathogens, and may be involved in damaging and eliminating digenean larvae. Thioredoxin-related protein of 14 kDa (TRP14) is a member of the Trx superfamily, and plays an important role in the scavenging of ROS. This study was designed to identify and characterize TRP14 from O. hupensis (OhTRP14), and investigate the involvement of OhTRP14 in the scavenging of ROS in snail host immune response to the parasite S. japonicum. Here we expressed and purified the recombinant OhTRP14 and its mutant, and rOhTRP14 displayed oxidoreductase activity dependent on the CPDC motif. OhTRP14 protein was ubiquitously present in all the tested snail tissues, and especially immunolocalized in the cytoplasm of immune cell types (hemocytes). Both the expression of OhTRP14 and ROS level increased significantly in snails following challenge with S. japonicum. The dsRNA-mediated knockdown of OhTRP14 was successfully conducted by oral feeding, and ROS production was increased by OhTRP14 knockdown, implying that OhTRP14 was involved in the scavenging of ROS in O. hupensis circulating hemocytes. Therefore, we conclude that OhTRP14 may be involved in the scavenging of ROS in snail host immune response to the parasite S. japonicum. The results expand our understanding of the interaction between this parasite and host, and lay a foundation for the establishment of Oncomelania-schistosome infection models.

Biological activities and functional analysis of macrophage migration inhibitory factor in Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

Schistosomiasis is a destructive parasitic zoonosis caused by agents of the genus Schistosoma, which afflicts more than 250 million people worldwide. The freshwater amphibious snail Oncomelania hupensis serves as the obligate intermediate host of Schistosoma japonicum. Macrophage migration inhibitory factor (MIF) has been demonstrated to be a pleiotropic immunoregulatory cytokine and a key signaling molecule involved in adaptive and innate immunity. In the present study, we obtained the full-length cDNA of OhMIF and analyzed the characteristics of the ORF and the peptide sequence in O. hupensis. Next we have successfully expressed and purified the recombinant OhMIF protein (rOhMIF) together with a site-directed mutant rOhMIFP2G, in which the N-terminal Proline (Pro2) was substituted by a Gly. Our results indicated that rOhMIF displayed the conserved D-dopachrome tautomerase activity which is dependent on Pro2, and this enzymatic activity can be significantly inhibited by the MIF antagonist ISO-1. Moreover, we also measured and compared the steady state kinetic values for D-dopachrome tautomerase activity of rOhMIF and rHsMIF, and the results showed that the reaction rate, catalytic efficiency and substrate affinity of rOhMIF are significantly lower than those of rHsMIF. Additionally, we also showed that rOhMIF had the oxidoreductase activity which can utilize DTT as reductant to reduce insulin. Furthermore, the results obtained from the in vitro injection assay demonstrated that rOhMIF and its mutant rOhMIFP2G can also induce the phosphorylation and activation of ERK1/2 pathway in O. hupensis circulating hemocytes, indicating that the tautomerase activity is not required for this biological function. These results are expected to produce a better understanding of the internal immune defense system in O. hupensis, and help to further explore the interaction between O. hupensis and its natural parasite S. japoniucm.

Identification and functional characterization of Oncomelania hupensis macrophage migration inhibitory factor involved in the snail host innate immune response to the parasite Schistosoma japonicum.

Schistosomiasis, caused by parasitic trematodes of the genus Schistosoma, remains a devastating public health problem, with over 200 million people infected and 779 million people at risk worldwide, especially in developing countries. The freshwater amphibious snail Oncomelania hupensis is the obligate intermediate host of Schistosoma japonicum. This unique and long-standing host-parasite interaction highlights the biomedical importance of the molecular and cellular mechanisms involved in the snail immune defense response against schistosome infection. In recent years, a number of immune-related effectors and conserved signalling pathways have been identified in molluscs, especially in Biomphalaria glabrata, which is an intermediate host for Schistosoma mansoni, but few have been reported in O. hupensis. Here we have successfully identified and functionally characterized a homologue of mammalian macrophage migration inhibitory factor (MIF) from O. hupensis (OhMIF). MIF, a pleiotropic regulator of innate immunity, is a constitutively expressed mediator in the host's antimicrobial defense system and stress response that promotes the pro-inflammatory functions of immune cells. In the present study, we detected the distribution of OhMIF in various snail tissues, especially in immune cell types (hemocytes) and found that OhMIF displays significantly increased expression in snails following challenge with S. japonicum. Knockdown of OhMIF was conducted successfully in O. hupensis and significantly reduced the percentage of phagocytic cell populations in circulating hemocytes. Furthermore, OhMIF is not only implicated in the activation and differentiation of hemocytes, but also essential to promote the migration and recruitment of hemocytes towards the infected sites. These results provide the first known functional evidence in exploring the molecular mechanisms involved in the O. hupensis innate immune defense response to the parasite S. japonicum and help to better understand the complex host-parasite interaction.