Parasites of the liver - epidemiology, diagnosis and clinical management in the European context.

Parasites in the liver cause significant global morbidity and mortality, as they can lead to recurrent cholangitis, cirrhosis, liver failure and cancer. Due to climate change and globalisation, their incidence is increasing, especially in Europe. The correct diagnosis of a hepatic parasite is often delayed because clinicians are unfamiliar with respective entities. Therefore, in this review, we aim to provide clinicians with a comprehensive clinical picture of hepatic parasites and to bring these neglected parasitic liver diseases to the wider attention of hepatology stakeholders in Europe and around the world.

Positive consequences of splenectomy for patients with schistosomiasis-induced variceal bleeding.

BACKGROUND: Patients with hepatic schistosomiasis are at high risk of gastroesophageal variceal bleeding, which is highly torrential and life threatening. This study aimed to assess the effects of splenectomy on patients with schistosomiasis-induced variceal bleeding, especially those influences related to overall survival (OS) rate. METHODS: From January 2005 to December 2018, 112 patients with schistosomiasis-induced varices were enrolled. In that period, all the patients with hepatic schistosomiasis who received endoscopic treatment for primary and secondary prophylaxis of gastroesophageal variceal bleeding were found eligible. The patients were divided into splenectomized group (n = 44, 39.3%) and control group (n = 68, 60.7%). RESULTS: Multivariate regression analysis of OS showed that splenectomy, hepatic carcinoma, and times of endoscopic treatment were independent prognostic factors for OS. Kaplan-Meier analysis revealed that the 5-year OS rate was 82.7% in splenectomized group versus 53.2% in control group (P = 0.037). The rate of no recurrence of variceal bleeding during 5-year (56.8% vs. 47.7%, P = 0.449) indicated that there was no significant difference between the two groups. Patients who received splenectomy had increased risk of portal vein thrombosis (52.3% vs. 29.4%, P = 0.012) and decreased proportion of severe ascites (20.5% vs 50.0%, P = 0.002). CONCLUSION: Splenectomy prior to endoscopic treatment provides a superior long-term survival for patients with schistosomiasis-induced variceal bleeding.

Prospects for liver fluke vaccines.

Fasciola spp., Opisthorchis spp. and Clonorchis sinensis are common liver flukes that can cause a variety of diseases, mainly cholangiocarcinoma induced by clonorchiasis and liver damage and associated pathology induced by fascioliasis. Because these trematodes are parasites of humans and domestic animals, they have greatly affected the economy of agricultural industries and public health worldwide. Due to the emergence of drug resistance and the living habits of flukes, among other reasons, a possibility of reinfection remains even when antiparasitic drugs are used. Therefore, developing a safe, efficient and cost-effective vaccine against trematodes is an important goal. Here, we briefly describe the progress in the development of vaccines against liver flukes. Related innovations may provide effective protection against these helminths and the diseases that they cause.

Hepatic Capillaria hepatica (Bancroft, 1893) infection in cat (Felis catus)-histopathological findings and first report from Iran.

Capillaria hepatica (syn. Calodium hepaticum) is a globally distributed nematode with a high affinity to the liver of a wide range of mammalian hosts, including humans. Documented reports of the nematode in cats and associated histopathology are rare. Here, we describe a case of C. hepatica infection in a 5-year-old male stray cat from Iran. At post-car accident necropsy, all body parts appeared normal except for the liver, in which a few yellowish-white granulomatous nodules were observed through the capsule and in the organ. Histopathological examination of the tissue revealed a large number of clustered parasite eggs in the parenchyma. The barrel-shaped, un-embryonated eggs (55.19 × 28.37 µm), with inconspicuous caps at both ends, were covered with striated shells. The presence of ova in the liver tissue had resulted in the development of hepatic inflammation with hepatocellular necrosis associated with the development of multifocal granulomas. As predators of small rodents, the cats might have a significant role in the epidemiology of C. hepatica. Infection of hosts through ingestion of embryonated eggs in contaminated water, food, or soil is of major importance in the epidemiology of C. hepatica. Since the rare reports of feline infection have come mainly from accidental detection of the parasite, any hepatic disease presenting difficulties to find an etiological agent may virtually be associated with the infection with this little-known nematode.

Genetic algorithms identify individuals with high risk of severe liver disease caused by schistosomes.

Schistosomes induce severe hepatic disease, which is fatal in 2-10% of cases, mortality being higher in cases of co-infection with HBV or HCV. Hepatic disease occurs as a consequence of the chronic inflammation caused by schistosome eggs trapped in liver sinusoids. In certain individuals, the repair process leads to a massive accumulation of fibrosis in the periportal spaces. We and others have shown that genetic variants play a crucial role in disease progression from mild to severe fibrosis and explain why hepatic fibrosis progresses rapidly in certain subjects only. We will review here published findings concerning the strategies that have been used in the analysis of hepatic fibrosis in schistosome-infected individuals, the genetic variants that have associated with fibrosis, and variants in new pathways crucial for fibrosis progression. Together, these studies show that the development of fibrosis is under the tight genetic control of various common variants with moderate effects. This polygenic control has made it possible to develop models that identify schistosome-infected individual at risk of severe hepatic disease. We discuss the performances and limitations of these models.

Prophylactic versus therapeutic role of the transplanted CD34+ Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.

First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient.

Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.

In vitro anthelmintic effect of biologically synthesized silver nanoparticles on liver amphistome, Gigantocotyle explanatum.

In order to ensure global food security a rationale approach is required to control all those factors which directly or indirectly affect the food productivity. The neglected helminthic diseases alone are responsible for huge economic losses to the agrarian stakeholders. The problem is further compounded by the emerging drug resistance in flukes against the commonly used anthelmintics like triclabendazole. Therefore, the search for alternatives including the nano-based approaches has become a necessity to develop future control strategies. In the present study the effect of biologically synthesized silver nanoparticles (AgNPs) was investigated on an economically important amphistome parasite, Gigantocotyle explanatum, obtained from the infected liver of the Indian water buffaloes, Bubalus bubalis. In vitro treatment of the adult worms with different doses of AgNPs severely affected the worm motility and caused ROS mediated damages in the treated flukes. The antioxidant system and the detoxification ability of the worms appeared to be disrupted along with pronounced DNA damage in the treated worms as compared to the controls. Following the treatment of worms with different concentrations of AgNPs there was a significant (p < 0.05) increase in lipid peroxidation and protein carbonylation levels which are the key oxidative stress markers. The tegumental surface which is metabolically active, was severely damaged as evident from the loss of papillae, severe blebbing, shearing and erosion of the surface structures. Such topographical disruptions would facilitate the penetration of the nanoparticles deep within the tissues that might greatly reduce the invasive potential of the flukes as evident from the decreased motility. Taken together our findings suggest that the AgNPs posses great anthelmintic potential and could be further exploited for the development of anthelmintic formulations which may be tested in vivo.

Nonspecific CD8+ T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8+ T Cell-Mediated Clusters against Malaria Liver-Stage Infection.

CD8+ T cells are the major effector cells that protect against malaria liver-stage infection, forming clusters around Plasmodium-infected hepatocytes and eliminating parasites after a prolonged interaction with these hepatocytes. We aimed to investigate the roles of specific and nonspecific CD8+ T cells in cluster formation and protective immunity. To this end, we used Plasmodium berghei ANKA expressing ovalbumin as well as CD8+ T cells from transgenic mice expressing a T cell receptor specific for ovalbumin (OT-I) and CD8+ T cells specific for an unrelated antigen, respectively. While antigen-specific CD8+ T cells were essential for cluster formation, both antigen-specific and nonspecific CD8+ T cells joined the clusters. However, nonspecific CD8+ T cells did not significantly contribute to protective immunity. In the livers of infected mice, specific CD8+ T cells expressed high levels of CD25, compatible with a local, activated effector phenotype. In vivo imaging of the liver revealed that specific CD8+ T cells interact with CD11c+ cells around infected hepatocytes. The depletion of CD11c+ cells virtually eliminated the clusters in the liver, leading to a significant decrease in protection. These experiments reveal an essential role of hepatic CD11c+ dendritic cells and presumably macrophages in the formation of CD8+ T cell clusters around Plasmodium-infected hepatocytes. Once cluster formation is triggered by parasite-specific CD8+ T cells, specific and unrelated activated CD8+ T cells join the clusters in a chemokine- and dendritic cell-dependent manner. Nonspecific CD8+ T cells seem to play a limited role in protective immunity against Plasmodium parasites.

A case of hepatic anisakiasis caused by Pseudoterranova decipiens mimicking metastatic liver cancer.

BACKGROUND: Anisakid nematodes (Anisakis spp. or Pseudoterranova spp.) usually infect gastric or intestinal walls, while they rarely infect in extra-gastrointestinal sites of human body. Generally, Anisakis spp. larvae are highly infected in fish intermediate hosts, whereas Pseudoterranova spp. larvae are very rarely infected. To the best of our knowledge, there have been no reports which have documented cases of hepatic anisakiasis caused by Pseudoterranova spp. This report describes the first documented case of hepatic anisakiasis due to infection with Pseudoterranova decipiens and clinical features of the hepatic anisakiasis through literature review. CASE PRESENTATION: The case was a 28-year-old man with prior history of malignancy who was found to have a hepatic mass mimicking metastatic liver tumor. A new low density area of 20 mm in diameter in liver segment 7 was found on follow-up CT. With suspicious diagnosis of metastatic liver cancer, laparoscopic partial hepatectomy was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with eosinophil infiltration and the presence of a larva with Y-shaped lateral cords, which are specific to anisakid larvae. The type of larva was identified as Pseudoterranova decipiens sensu lato using PCR of DNA purified from a fixed granuloma embedded in paraffin. CONCLUSION: The present report is the first to discuss the case of a patient with hepatic anisakiasis caused by Pseudoterranova decipiens. Hepatic anisakiasis is a potential differential diagnosis for hepatic tumors and genetic identification with the PCR method was reliable for obtaining final diagnosis even when the larvae body in the resected specimen collapses with time.

Surgical portosystemic shunts versus devascularisation procedures for prevention of variceal rebleeding in people with hepatosplenic schistosomiasis.

BACKGROUND: Hepatosplenic schistosomiasis is an important cause of variceal bleeding in low-income countries. Randomised clinical trials have evaluated the outcomes of two categories of surgical interventions, shunts and devascularisation procedures, for the prevention of variceal rebleeding in people with hepatosplenic schistosomiasis. The comparative overall benefits and harms of these two interventions are unclear. OBJECTIVES: To assess the benefits and harms of surgical portosystemic shunts versus oesophagogastric devascularisation procedures for the prevention of variceal rebleeding in people with hepatosplenic schistosomiasis. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, LILACS, reference lists of articles, and proceedings of relevant associations for trials that met the inclusion criteria (date of search 11 January 2018). SELECTION CRITERIA: Randomised clinical trials comparing surgical portosystemic shunts versus oesophagogastric devascularisation procedures for the prevention of variceal rebleeding in people with hepatosplenic schistosomiasis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials and extracted data using methodological standards expected by Cochrane. We assessed risk of bias according to domains and risk of random errors with GRADE and Trial Sequential Analysis. We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We found two randomised clinical trials including 154 adult participants, aged between 18 years and 65 years, diagnosed with hepatosplenic schistosomiasis. One of the trials randomised participants to proximal splenorenal shunt versus distal splenorenal shunt versus oesophagogastric devascularisation with splenectomy, and the other randomised participants to distal splenorenal shunt versus oesophagogastric devascularisation with splenectomy. In both trials the diagnosis of hepatosplenic schistosomiasis was made based on clinical and biochemical assessments. The trials were conducted in Brazil and Egypt. Both trials were at high risk of bias.We are uncertain as to whether surgical portosystemic shunts improved all-cause mortality compared with oesophagogastric devascularisation with splenectomy due to imprecision in the trials (risk ratio (RR) 2.35, 95% confidence interval (CI) 0.55 to 9.92; participants = 154; studies = 2). We are uncertain whether serious adverse events differed between surgical portosystemic shunts and oesophagogastric devascularisation with splenectomy (RR 2.26, 95% CI 0.44 to 11.70; participants = 154; studies = 2). None of the trials reported on health-related quality of life. We are uncertain whether variceal rebleeding differed between surgical portosystemic shunts and oesophagogastric devascularisation with splenectomy (RR 0.39, 95% CI 0.13 to 1.23; participants = 154; studies = 2). We found evidence suggesting an increase in encephalopathy in the shunts group versus the devascularisation with splenectomy group (RR 7.51, 95% CI 1.45 to 38.89; participants = 154; studies = 2). We are uncertain whether ascites and re-interventions differed between surgical portosystemic shunts and oesophagogastric devascularisation with splenectomy. We computed Trial Sequential Analysis for all outcomes, but the trial sequential monitoring boundaries could not be drawn because of insufficient sample size and events. We downgraded the overall certainty of the body of evidence for all outcomes to very low due to risk of bias and imprecision. AUTHORS' CONCLUSIONS: Given the very low certainty of the available body of evidence and the low number of clinical trials, we could not determine an overall benefit or harm of surgical portosystemic shunts compared with oesophagogastric devascularisation with splenectomy. Future randomised clinical trials should be designed with sufficient statistical power to assess the benefits and harms of surgical portosystemic shunts versus oesophagogastric devascularisations with or without splenectomy and with or without oesophageal transection.

Hepatic Dicrocoelium dendriticum infection in a miniature horse.

A miniature horse which died following humane seizure from an Ontario farm was emaciated with serous atrophy of fat. Autopsy revealed hepatic atrophy and moderate periportal fibrosis. Eggs and trematodes seen in the liver were identified as Dicrocoelium dendriticum. This appears to be the first reported case of infection of equids in North America with Dicrocoelium dendriticum.

Infection parDicrocoelium dendriticumhépatique chez un cheval miniature. Un cheval miniature qui est mort à la suite d'une saisie humanitaire dans une ferme de l'Ontario était émacié et avait une atrophie séreuse des tissus adipeux. L'autopsie a révélé une atrophie hépatique et une fibrose périportale modérée. Des oeufs et des trématodes observés dans le foie ont été identifiés comme Dicrocoelium dendriticum. Il semblerait qu'il s'agit du premier cas signalé d'infection des équidés par Dicrocoelium dendriticum en Amérique du Nord.(Traduit par Isabelle Vallières).

[Visceral parasitic migration of liver: a clinicopathologic analysis of seven cases].

Objective: To investigate the clinical, radiological and pathological features of visceral parasitic migration of the liver. Methods: Seven cases of visceral parasitic migration of liver were identified at the Affiliated Drum Tower Hospital of Medical School of Nanjing University from January 2008 to July 2017. Clinical data, enhanced CT image and pathological features were analyzed, combining with literature review. Results: There were 5 male and 2 female patients. Five patients presented with abdominal pain or discomfort as the first symptom. Two patients were admitted to the hospital for physical examination with liver nodule. Blood eosinophils were mildly to moderately increased in 4 cases. Enhanced CT showed the liver irregular beaded nodules that showed no significant enhancement of arterial phase. Mild enhancement of round lesions (ring lesion) was seen in a few cases before surgery. By histopathology, the lesions showed central geographic necrosis, surrounded by epithelioid granuloma and inflammatory cell bands. A large number of eosinophils and scattered multinucleated giant cells were found, especially at the peripheral of the lesion. Charcot-Leyden crystals were present in all case and parasitic migrans was found in one case. Conclusions: Visceral parasitic migration of liver is a rare liver disease and is easily misdiagnosed as other benign or malignant liver tumors. Combining clinical data, enhanced CT images and pathological examination can improve the preoperative and postoperative diagnosis of the disease.

S. mansoni-T. cruzi co-infection modulates arginase-1/iNOS expression, liver and heart disease in mice.

Although Schistosoma species and Trypanosoma cruzi share common endemic areas, co-infections by these parasites remains overlooked. By using a murine model of S. mansoni and T. cruzi co-infection, we investigated if and to what extent these infections might interact to change the pathological outcomes typically observed when the host is infected by a single parasite species. Swiss mice were randomized into four groups: uninfected (NI) and those infected by S. mansoni (SM), T. cruzi (TC) or co-infected (SM + TC). After 120 days of S. mansoni infection, T. cruzi was concurrently inoculated and the infection occurred for 30 days. Taken together, we identified that the overlap of Th2 (schistosomiasis) and Th1 (Chagas disease) immunological patterns changes the host resistance against both pathogens. Beyond impairing the control of granulomatous inflammation, T. cruzi parasitemia and parasitism in co-infected animals, the Th2 inflammatory response against S. mansoni elicits the activation of the arginase-1 pathway to the detriment of inducible oxide nitric synthase (iNOS) expression and nitric oxide (NO) production, contributing to the liver damage, with minor effects on heart pathology.

Antioxidant defense of Nrf2 vs pro-inflammatory system of NF-κB during the amoebic liver infection in hamster.

Entamoeba histolytica is the causative agent of amoebic liver abscess (ALA), which course with an uncontrolled inflammation and nitro-oxidative stresses, although it is well known that amoeba has an effective defence mechanisms against this toxic environment, the underlying molecular factors responsible for progression of tissue damage remain largely unknown. The purpose of the present study was to determine during the acute stage of ALA in hamsters, the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-kappa B (NF-κB), which are activated in response to oxidative stress. From 12 h post-infection the ALA was visible, haematoxylin-eosin and Masson's trichrome stains were consistent with these observations, and alanine aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase serum activities were increased too. At 48 h after infection, liver glycogen content was significantly reduced. Western blot analyses showed that 4-Hydroxy-2-nonenal peaked at 12 h, while glycogen synthase kinase-3ß, cleaved caspase-3, pNF-κB, interleukin-1ß and tumour necrosis factor-α were overexpressed from 12 to 48 h post-infection. Otherwise, Nrf2 and superoxide dismutase-1, decreased at 48 h and catalase declined at 36 and 48 h. Furthermore, heme oxygenase-1 was increased at 12 and 24 h and decreased to normal levels at 36 and 48 h. These findings suggest for the first time that the host antioxidant system of Nrf2 is influenced during ALA.

Hepatic paragonimiasis in a 15-month-old girl: a case report.

BACKGROUND: Paragonimiasis, particularly hepatic paragonimiasis (HP), is a type of zoonotic parasitic disease rarely encountered in infants. There have been only a few reports of HP, and no case of HP has been reported in an infant. CASE PRESENTATION: A 15-month-old girl presented with persistent mild fever with a duration of 1 month, hepatomegaly, and low-density lesions in the right hepatic lobe on abdominal ultrasound and computer tomography. Pathological examination and serum antibody detection were performed to verify HP. The diagnosis of HP was established based on findings of Charcot-Leyden crystals on liver lesion biopsy and antibodies against paragonimus westermani detected by enzyme-linked immunosorbent assay. After initiation of praziquantel (75 mg/kg/day for 3 days), all clinical findings promptly improved and the patient was discharged. CONCLUSION: It is very important to consider paragonimiasis in the clinical examination of infants from an area with paragonimiasis epidemic presenting with fever, hepatomegaly, low-density lesions in the liver.

Molecular and phylogenetic analyses of the liver amphistome Explanatum explanatum (Creplin, 1847) Fukui, 1929 in ruminants from Bangladesh and Nepal based on nuclear ribosomal ITS2 and mitochondrial nad1 sequences.

Explanatum explanatum flukes, liver amphistomes of ruminants, cause significant economic loss in the livestock industry by inducing severe liver damage. A total of 66 flukes from 26 buffaloes and 7 cattle in four different geographic areas of Bangladesh and 20 flukes from 10 buffaloes in the Chitwan district of Nepal were subjected for analysis. The sequences (442 bp) of the second internal transcribed spacer (ITS2) of ribosomal DNA and the variable fragments (657 bp) of mitochondrial nicotinamide dehydrogenase subunit 1 (nad1) of E. explanatum flukes from Bangladesh and Nepal were analysed. The aim of this study was molecular characterization of the flukes and to elucidate their origin and biogeography. In the ITS2 region, two genotypes were detected among the flukes from Bangladesh, while flukes from Nepal were of only one genotype. Phylogenetic analyses inferred from the nad1 gene revealed that at least four divergent populations (groups I-IV) are distributed in Bangladesh, whereas two divergent populations were found to be distributed in Nepal. Fst values (pairwise fixation index) suggest that Bangladeshi and Nepalese populations of group I to IV are significantly different from each other; but within groups III and IV, the populations from Bangladesh and Nepal were genetically close. This divergence in the nad1 gene indicates that each lineage of E. explanatum from diverse geography was co-adapted during the multiple domestication events of ruminants. This study, for the first time, provides molecular characterization of E. explanatum in Bangladesh and Nepal, and may provide useful information for elucidating its origin and dispersal route in Asia.

IL-23 prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage.

BACKGROUND & AIMS: The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, Entamoeba histolytica. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite-induced liver damage. METHODS: IL-23p19(-/-), IL-17A/F(-/-), CCR2(-/-), and wild-type (WT) mice were intra-hepatically infected with E. histolytica trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. Liver-specific gene and protein expression during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in IL-23p19(-/-) and WT mice to investigate the role of IL-13 in disease outcome. RESULTS: Liver damage in infected IL-23p19(-/-), IL-17A/F(-/-), and CCR2(-/-) mice was strongly attenuated compared with that in WT mice. IL-23p19(-/-) mice showed reduced accumulation of IL-17 and CCL2 mRNA and proteins. Increased numbers of IL-13-producing CD11b(+)Ly6C(lo) monocytes were associated with disease attenuation in IL-23p19(-/-) mice. Immuno-depletion of IL-13 in IL-23p19(-/-) mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery. CONCLUSIONS: The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL-13 secreted by CD11b(+)Ly6C(lo) monocytes may be associated with recovery from liver damage. An IL-13/anti-IL13-mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage.

Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.

Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.