Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection.

In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8+ T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids. Exploring the requirements for liver Trm cell induction, we showed that by combining dendritic cell-targeted priming with liver inflammation and antigen recognition on hepatocytes, high frequencies of Trm cells could be induced and these cells were essential for protection against malaria sporozoite challenge. Our study highlights the immune potential of liver Trm cells and provides approaches for their selective transfer, expansion, or depletion, which may be harnessed to control liver infections or autoimmunity.

TLR9 signalling inhibits Plasmodium liver infection by macrophage activation.

Recognition of pathogen-associated molecular patterns (PAMPs) through Toll-like receptors (TLRs) plays a pivotal role in first-line pathogen defense. TLRs are also likely triggered during a Plasmodium infection in vivo by parasite-derived components. However, the contribution of innate responses to liver infection and to the subsequent clinical outcome of a blood infection is not well understood. To assess the potential effects of enhanced TLR-signalling on Plasmodium infection, we systematically examined the effect of agonist-primed immune responses to sporozoite inoculation in the P. berghei/C57Bl/6 murine malaria model. We could identify distinct stage-specific effects on the course of infection after stimulation with two out of four TLR-ligands tested. Priming with a TLR9 agonist induced killing of pre-erythrocytic stages in the liver that depended on macrophages and the expression of inducible nitric oxide synthase (iNOS). These factors have previously not been recognized as antigen-independent effector mechanisms against Plasmodium liver stages. Priming with TLR4 and -9 agonists also translated into blood stage-specific protection against experimental cerebral malaria (ECM). These insights are relevant to the activation of TLR signalling pathways by adjuvant systems of antimalaria vaccine strategies. The protective role of TLR4-activation against ECM might also explain some unexpected clinical effects observed with pre-erythrocytic vaccine approaches.

Eosinophils participate in modulation of liver immune response and tissue damage induced by Schistosoma mansoni infection in mice.

The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-ß and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.

Bevacizumab as a potential anti-angiogenic therapy in schistosomiasis: A double-edged, but adjustable weapon.

AIM: Investigating the anti-angiogenic effect of bevacizumab on chronic schistosomiasis mansoni in a trial to hinder the Schistosome-induced angiogenesis and porto-systemic shunting complications. METHODS: The immunohistochemical expression of CD34, VEGF-R1, PCNA and α-SMA (angiogenesis markers) was analysed in the lung, liver and gastrointestinal junctions of chronic S mansoni infected mice after intraperitoneal injection of bevacizumab. The effect of prolonged administration of bevacizumab with praziquantel was also assessed through parasitic load, protective index, granuloma and fibrous tissue evaluation. RESULTS: A regression in the vascular activity and microvascular density was observed in the infected mice after receiving bevacizumab. They had a significantly less VEGF-R1, PCNA, CD-34 and α-SMA expression in comparison to the infected untreated mice. The least tissue egg count was reported in mice received bevacizumab for 6 weeks (Mean = 27 120). However, they had persistent liver granulomas, and massively amalgamated fibrosis. Interestingly, the least faecal egg and tissue worms counts (Mean = 112, 13.4), and the highest protection index (39.26) were reported in mice received bevacizumab for 3 weeks, with marked granuloma, and fibrous tissue resolution. CONCLUSIONS: Bevacizumab has a promising protective effect against the Schistosoma-induced angiogenesis. As an adjuvant to praziquantel, it is important to adjust the appropriate duration of administration that achieves the best schistosomicidal effect without impeding granuloma and fibrous tissue resolution.

Hepatic Coccidiosis in Triportheus angulatus Spix & Agassiz, 1829 (Characiformes: Triportheidae), a Tropical Fish from the Eastern Brazilian Amazon, with the Description of a New Species of Calyptospora (Apicomplexa: Calyptosporidae).

Hepatic infection involving a parasite of the family Calyptosporidae was recorded in characiform fish from the Tocantins river in the Brazilian Amazon region. In the present study, an integrated comparative analysis of morphological characteristics, histological and structural traits, and the sequence of a partial fragment of the SSUrRNA gene provides support for the identification of a new calyptosporid species, found parasitising the hepatic tissue of the fish Triportheus angulatus, collected from the Tocantins River. This new species was named Calyptospora gonzaguensis n. sp. and had ovoid oocysts with a diameter of 19.6 ± 1.4 µm and four peripheral sporocysts, 9.2 ± 0.6 µm long and 3.9 ± 0.2 µm wide, enveloped individually in fine adhesive membrane, composed of an ellipsoid body and posterior extension, with a mean length of 2.2 ± 0.4 µm.

Beyond pyogenic liver abscess: a comprehensive review of liver infections in emergency settings.

Hepatobiliary infections are commonly encountered in emergency settings ranging from common pathology such as pyogenic abscess to relatively uncommon and rare etiologies. Since extensive literature is already available on imaging of more common bacterial infections, for the sake of focused discussion, this review will discuss radiological appearance of less commonly encountered hepatic infections of fungal, parasitic, viral, and tubercular etiologies. Epidemiological and clinical information remain extremely important for obtaining more accurate presumptive diagnosis. In the era of diverse population migration, a modern-era radiologist must be well versed about the imaging spectrum of liver infections.

Friomaramide, a Highly Modified Linear Hexapeptide from an Antarctic Sponge, Inhibits Plasmodium falciparum Liver-Stage Development.

The cold waters of Antarctica are known to harbor a rich biodiversity. Our continuing interest in the chemical analysis of Antarctic invertebrates has resulted in the isolation of friomaramide (1), a new, highly modified hexapeptide, from the Antarctic sponge Inflatella coelosphaeroides. The structure of friomaramide was determined using spectroscopic methods and its configuration established by Marfey's method. Friomaramide, which bears the unusual permethylation of the amino acid backbone and is the longest polypeptide bearing a tryptenamine C-terminus, blocks >90% of Plasmodium falciparum liver-stage parasite development at 6.1 µM.

Niosomes for enhanced activity of praziquantel against Schistosoma mansoni: in vivo and in vitro evaluation.

Praziquantel (PZQ) is recommended by the WHO as the first line in treatment of schistosomiasis. Unfortunately, it exhibits low oral bioavailability which can compromise its efficacy. Nanostructures showed promising potential to overcome this problem. Accordingly, the aim of this study was to investigate the effect of niosomal encapsulation of PZQ on its activity on Schistosoma mansoni in vitro and in vivo. PZQ was encapsulated in niosomal formulation comprising span 60, cholesterol with peceol being included as absorption enhancer. The in vitro work determined the schistosomicidal activity and morphological changes after incubation with drug solution or PZQ-niosomes. The in vivo study utilized infected mice which received PZQ orally as solution or as niosomes. The activity was assessed by monitoring egg and worm count in addition to histopathological and immunohistochemical studies. The in vitro studies revealed that niosomes alone caused a 30% death of adult parasites and caused completely coiled body, destruction, and peeling of tubercles and spines, with flattening and effacement of gynecophoric canal, blebbing with niosomes vesicles attached to it. Niosomes containing PZQ at a concentration of 0.001 µg/ml increased the death from 30 to 50% with the corresponding PZQ solution causing only 10% death. The in vivo study reflected of niosome-PZQ over PZQ solution as indicated from significant reduction of adult worm count, hepatic and intestinal egg depositions, hepatic granuloma size, and numbers, with marked reduction of vascular endothelial growth factor expression. The study introduced niosomes as promising carriers for enhanced activity of PZQ.

[A Rare Complication of Acute Diarrhae Caused by Cryptosporidium: Possible Hepatobiliary System Involvement in a Child without Immunodeficiency]. / Akut Cryptosporidium Ishalinin Nadir Bir Komplikasyonu: Immün Yetmezlik Bulunmayan Çocuk Olguda Olasi Hepatobiliyer Tutulum.

Cryptosporidium spp. is one of the leading causes of parasitic diarrhea. It is the most common parasite in humans all over the world with Giardia. Cryptosporidium is an important cause of chronic diarrhea in Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) patients. Patients with normal immune system may have an asymptomatic course or clinical presentation such as acute watery diarrhea without blood and persistent diarrhea. The severity and duration of the disease may be a reflection of the immune deficiency. Children under two years of age and children with malnutrition may have a risk of prolonged Cryptosporidium spp. infection, even if immunodeficiency work-up is normal, as they may have defects in the natural immune system and lymphocyte functions. Cryptosporidium spp. oocysts contaminate water sources, swimming pools, vegetables and fruits because oocysts are partially resistant to chlorination. So it may be problem for public health. Pets, livestock and humans can be carriers of Cryptosporidium spp. Factors such as developmental level of the countries, immune system, nutritional status, living in crowded environments, contact with contaminated water, close contact with animals, working at a hospital and hot and humid climate affect the incidence of Cryptosporidiosis. Cryptosporidium spp. may cause asymptomatic infection, mild diarrheal disease or severe diarrhea with high volume, which may be accompanied by nausea, vomiting, abdominal pain and fever, following a 1-7 day incubation period. Diarrhea may be acute or chronic, transient, intermittent, or continuous; loss of fluid can be up to 25 L/day in severe diarrhea. Cryptosporidium spp. are mainly located in intestines, but non-intestinal (bile ducts, pancreas, stomach, respiratory system, kidney) involvement may occur in immunocompromised patients. Hepatobiliary system involvement occurs in 10-30% of patients with AIDS; stone-free cholecystitis can lead to sclerosing cholangitis and pancreatitis. Hepatobiliary involvement is not expected in patients without immunodeficiency. In this article, we present a case of Cryptosporodiosis with hepatobiliary system involvement who were admitted to the pediatric emergency clinic with the complaints of severe diarrhea and Cryptosporidium spp. oocysts were detected in parasitological examination of the stool specimen. Immunodeficiency was not considered with her resume and laboratuary examinations. We would like to emphasize that Cryptosporodium spp. may be the cause of severe acute diarrhea in non-immunocompromised patients and may also involve hepatobiliary system involvement.

Pathology and Plasma Biochemistry of Common Eider (Somateria mollissima) Males Wintering in the Danish Part of the Western Baltic.

Blood biochemistry, body mass, and gross pathology of male eiders (Somateria mollissima) wintering in the Inner Danish Waters of the western Baltic Sea (the Great Belt Strait) were assessed in this study. In November 2015, 14 specimens were obtained from the area defined for examination. Of the subject animals captured, 1 had dilated intestines and 2 had granulomas with encapsulated shotgun pellets considered to be chronic in nature. All 14 males were determined to have enteritis along with acanthocephalan and trematode endoparasites. Compared with reference values for captive eiders, plasma values of alanine aminotransferase (93%), total bilirubin (45%), gamma-glutamyl transferase (41%), and alkaline phosphatase (92%) showed significant increases in all 14 male birds. Altogether, the plasma biochemistry and gross pathology findings suggest that up to as many as 20% of the eider males in the Inner Danish Waters of the western Baltic Sea may suffer from liver and bile duct lesions and enteritis. The overall effect on the bird's survival from the results of this investigation is unknown. Therefore, the authors emphasize that more research is required on wintering eiders in the western Baltic to obtain a better understanding of their overall health status during winter, as well as their responses to wound-related lesions associated with gunshot pellets.

Echinococcus granulosus cyst fluid enhances epithelial-mesenchymal transition.

Cystic echinococcosis is characterized by fluid-filled hydatid cysts in the liver and lungs. The cysts are surrounded by a host fibrous layer (the pericyst) which acts to isolate the parasite from surrounding tissues. Previous studies in liver cysts have indicated that the parasite may be a stimulating fibrosis. The aim of this study was to investigate whether hydatid cyst fluid (HCF) could influence the potential for fibrosis to occur in lung tissue by stimulating epithelial to mesenchymal transition (EMT) in a human lung epithelial cell line. An adenocarcinoma-derived alveolar basal epithelial cell line (A549) was used as a model for human alveolar epithelial cells (AEC II). These were cultured in vitro with HCF (UK sheep origin). Assays to investigate cell proliferation, cell migration and expression of cytoskeletal markers showed that HCF could stimulate changes indicative of EMT, including enhanced cell proliferation and migration; increased expression of mesenchymal cytoskeletal markers (fibronectin and vimentin) accompanied by a down-regulation of an epithelial marker (E-cadherin). Molecules within hydatid cyst fluid are capable of inducing phenotypic changes in A549 cells indicating that the parasite has the potential to modify lung epithelial cells which could contribute to fibrotic reactions.

Histopathological changes and oxidative damage in hepatic tissue of rats experimentally infected with Babesia bigemina.

The present study was aimed to investigate oxidative stress, DNA damage, and histopatholog- ical alterations in hepatic tissues of splenectomized Wistar rats experimentally infected with Ba- besia bigemina. Rats were challenged with 5x106 infected erythrocytes. Babesia infection was con- firmed both with Giemsa's staining blood smears and nested-PCR amplified region of apical membrane antigen-1 (AMA-1) gene. Parasitemia reached approximately 10 % at day 5 post-in- fection. Livers of infected rats were enlarged and darker in color, became extremely brittle with marked congestion. Microscopic evaluation showed cytoplasmic clearing of hepatocytes and se- vere hydropic changes with significantly dilated sinusoids containing macrophages and also intra- sinosoidal parasitized erythrocytes. Severe infiltration of lymphoplasma cells was also present throughout the liver parenchyma. Furthermore, Kupffer cells were enlarged and, occasionally, containing Babesia-parasitized erythrocytes. The activity of Glutathione (GSH) and catalase (CAT), and total antioxidant capacity (TAC) were also significantly decreased (p ⟨ 0.05) after infection of rats with B. bigemina. B. bigemina infection also induced a significant increase (p ⟨ 0.05) in hepatic malondialdehyde (MDA) and nitric oxide-derived products (NOx) concentra- tions as well as amount of endogenous hepatocytes DNA damage. Hepatic damage was also re- flected through the measurement of lactic acid dehydrogenase (LDH) and protein carbonyl con- tent (PCO) in liver cells. These two indices of liver injury were also significantly elevated (p ⟨ 0.5) during B. bigemina infection. Evaluation of correlation between assayed variables in infected rats revealed that MDA levels were positively correlated with PCO, NOx, LDH and DNA damage in the infected group and negatively correlated with GSH, CAT and TAC. There was also an inverse relationship between the antioxidant enzymes activities of GSH, CAT and TAC with PCO, NOx and DNA damage in infected rats. However, NOx showed positive correlation with PCO and DNA damage in infected rats. On the basis of the above results it can be concluded that the Ba- besia infection increases oxidative stress markers, protein carbonyl content and DNA damage and decreases antioxidant enzymes activities in the liver. These results suggest that B. bigemina infec- tion could alter the liver histopathology and causes DNA damage following oxidative stress in hepatic tissue. Further studies are needed to precisely define how hepatic tissue damage takes place in B. bigemina infection.

Seroepidemiology of Toxoplasma gondii infection in patients with liver disease in eastern China.

The role of the protozoan parasite Toxoplasma gondii in the pathogenesis of liver disease has recently gained much interest. The aim of this study was to determine the prevalence and risk factors associated with T. gondii infection in patients with liver disease from three cities in Shandong and Henan provinces, China. A case-control study was conducted from December 2014 to November 2015 and included 1142 patients with liver disease and 1142 healthy controls. Serum samples were collected from all individuals and were examined with enzyme-linked immunosorbent assay for the presence of anti-T. gondii IgG and IgM antibodies. Information on the demographics, clinical, and lifestyle characteristics of the participants was collected from the medical records and by the use of a questionnaire. The prevalence of anti-T. gondii IgG was 19·7% in patients with liver disease compared with 12·17% in the controls. Only 13 patients had anti-T. gondii IgM antibodies compared with 12 control individuals (1·14% vs. 1·05%, respectively). The highest seroprevalence was detected in patients with liver cancer (22·13%), followed by hepatitis patients (20·86%), liver cirrhosis patients (20·42%), and steatosis patients (20%). Multivariate logistic regression analysis indicated that consumption of raw meat (odds ratio (OR) = 1·32; 95% confidence interval (CI) 1·01-1·71; P = 0·03) and source of drinking water from wells (OR = 1·56; 95% CI 1·08-2·27; P = 0·01) were independent risk factors for T. gondii infection in liver disease patients. These findings indicate that T. gondii infection is more likely to be present in patients with liver disease. Therefore, efforts should be directed toward health education of populations at high risk of T. gondii infection and measures should be taken to protect vulnerable patients with liver disease.

Quantifying parasite presence in relation to biological parameters of harbour porpoises Phocoena phocoena stranded on the Dutch coast.

Harbour porpoises are often found to be infected by endoparasites in several organs including the lungs and stomach as well as the heart, liver and ears. Nevertheless there is still little knowledge about the impact, ecology, transmission, and virulence of these parasitic infections. Here, we profile the presence of parasites in 4 frequently infected organs (lungs, stomach, liver and ears) in relation to biological parameters of harbour porpoises stranded along the Dutch coastline between December 2008 and December 2013. We found that parasites were common, with prevalence of 68% in lungs, 74.4% in ears, 26% in stomach and 23.5% in liver. We used generalised linear models to further quantify parasite presence in relation to biological data gathered during necropsy (sex, body length and nutritive condition). Body length (used as a proxy for age) was significant in explaining parasite presence for all organs with increasing probability of having the parasite with increasing body length. For the parasitic infections in the ears and stomach the nutritive condition was an additional significant factor, with a higher probability of parasite presence in porpoises in a poorer nutritive condition. The results of this study can be used as a baseline for assessing parasite presence in harbour porpoises and are a first step towards linking parasite infections to basic biological data gathered during necropsy.

Immunoregulation in larval Echinococcus multilocularis infection.

Alveolar echinococcosis (AE) is a clinically very severe zoonotic helminthic disease, characterized by a chronic progressive hepatic damage caused by the continuous proliferation of the larval stage (metacestode) of Echinococcus multilocularis. The proliferative potential of the parasite metacestode tissue is dependent on the nature/function of the periparasitic immune-mediated processes of the host. Immune tolerance and/or down-regulation of immunity are a marked characteristic increasingly observed when disease develops towards its chronic (late) stage of infection. In this context, explorative studies have clearly shown that T regulatory (Treg) cells play an important role in modulating and orchestrating inflammatory/immune reactions in AE, yielding a largely Th2-biased response, and finally allowing thus long-term parasite survival, proliferation and maturation. AE is fatal if not treated appropriately, but the current benzimidazole chemotherapy is far from optimal, and novel options for control are needed. Future research should focus on the elucidation of the crucial immunological events that lead to anergy in AE, and focus on providing a scientific basis for the development of novel and more effective immunotherapeutical options to support cure AE by abrogating anergy, anticipating also that a combination of immuno- and chemotherapy could provide a synergistic therapeutical effect.

New insights into diagnosis of Platynosomum fastosum (Trematoda: Dicrocoeliidae) in cats.

Platynosomum fastosum is a hepatic trematode which causes the so-called lizard poisoning in cats. This parasite is reported in tropical and sub-tropical areas infecting the liver, gallbladder, and bile ducts of cats. Despite its clinical importance, the diagnosis of P. fastosum has been poorly investigated so far. In this study, three cases of infection by P. fastosum in cats are reported. The FLOTAC technique was utilized for the first time in the detection of eggs of this parasite. Three cats (two males and one female), being one of them with a history of diarrhea and vomiting, were diagnosed positive for the presence of P. fastosum eggs through the FLOTAC technique. In conclusion, this study provides important and new insights into the diagnosis of P. fastosum in cats, expanding the geographical knowledge of this parasite in Brazil.

The potential role of Punica granatum treatment on murine malaria-induced hepatic injury and oxidative stress.

Malaria is a health burden disease where the world harnessed the power of expertise and innovation to understand the biology of the parasite and the pathogenesis of the disease as well as to discover effective drugs. However, the treatment of malaria remains a challenging task and inadequate to address today's perplexing problem, the emergence of resistant strains. Historically, traditional medicine has been a mainstay for remediation and still retains its importance with the presence of potent natural products. Pomegranate has been used as antioxidant and anti-inflammatory against a range of diseases. Therefore, pomegranate peel extract (PPE) was used in this study to examine its effect on Plasmodium chabaudi-induced hepatic inflammation. Animals were allocated into three groups: a vehicle control group, a group infected with 10(6) P. chabaudi-parasitized erythrocytes and a pomegranate-treated group infected with 10(6) P. chabaudi-parasitized erythrocytes. This group received 100 µl of 300 mg/kg PPE after infection. The results showed the effectiveness of PPE on reversing the anaemic signs that have been provoked by P. chabaudi infection through instating the haemoglobin concentration and erythrocyte count back to normal values. Moreover, PPE exhibited hepatoprotective activities upon histopathological examination and liver function tests. These data were further confirmed by the significant reduction of the hepatic oxidative markers, glutathione, nitric oxide and malondialdehyde, in mice infected with P. chabaudi. Based on these outcomes, pomegranate could be used as a hepatoprotective agent against P. chabaudi-induced hepatic injury. However, further studies are needed in order to determine the mode of action of pomegranate upon infection.

HEPATIC LYMPHOMA AND SPLENIC ASPERGILLOSIS MIMICKING HEPATOSPLENIC ABSCESSES FROM MELIOIDOSIS IN THAILAND.

We report here a case of hepatic lymphoma and splenic aspergillosis in an elderly patient with diabetes mellitus, exhibiting hepatosplenic abscesses mimicking melioidosis. Immunohistochemistry confirmed the diagnosis of a diffuse hepatic large B-cell lymphoma. Biopsy of the spleen revealed a clump of fungus with a slender shape and dichotomous branching, morphologically consistent with aspergillosis. Hepatosplenic abscesses are a common presentation in melioidosis, but this case reveals this assumption can lead to misdiagnosis. Histological and microbiological confirmation are required, especially in patients with hepatosplenic lesions.

The effect of recombinant sTGFß1RII and sIL13Rα2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and signal transduction in a mouse model of schistosome disease.

This study was designed to investigate the effect of recombinant sTGFß1RII and sIL13Rα2 receptor proteins on schistosomiasis japonica, hepatic fibrosis and the expression of SMAD3 and STAT6. The proteins sTGFß1RII and sIL13Rα2 were expressed in Escherichiacoli, purified using affinity chromatography and characterized by Western blotting. Female BALB/C mice (48) were randomly divided into eight groups and infected with Schistosoma japonicum. Five weeks after infection, test groups were injected with the recombinant proteins at different doses. Eight weeks after infection, lung and hepatic tissue samples were obtained and stained with hematoxylin and eosin (HE) and Masson's trichrome. Immunohistochemical staining was used to detect the expression of SMAD3 and STAT6. The recombinant proteins sTGFß1RII and sIL13Rα2 were successfully expressed, purified, and characterized. The granuloma area, hepatic hydroxyproline (HYP) level and hepatic fibrosis of the protein therapeutic groups were significantly smaller than those of the positive control group (P<0.01). Treatment with sTGFß1RII was more effective when the protein was administered for 4weeks rather than 2 (P<0.01). Hepatic fibrosis in the groups using a low dose of protein sTGFß1 was lower that of the combination group (P<0.05). The expression level of STAT6 was significantly lower in groups treated with sIL13Rα2 than in groups not treated with the protein (P<0.01). The recombinant proteins TGFß1RII and sIL13Rα2 were able to decrease granuloma area and hepatic fibrosis in schistosomiasis japonica, and also reduced the expression of the signal transduction proteins SMAD3 and STAT6. The proteins were more effective when used in combination than when applied singly.