Tritrichomonas foetus is a protozoan parasite that causes bovine trichomonosis (also referred to as trichomoniasis) resulting in substantial economic loss in extensive grazing systems. The parasite colonises the reproductive tracts of both male and female cattle, being asymptomatic in males but causing early reproductive failure in infected females. This systematic review aimed to examine research manuscripts describing the development of T. foetus vaccines, the strategies employed, and the immune response associated with T. foetus infection. A systematic review was conducted using indexed sources on Scopus, PubMed, Web of Science, and Embase to search for published vaccine development studies in English utilising either experimental or commercial T. foetus vaccines for bovine trichomonosis. Search terms (cattle, bull, heifer, vaccine, immune response, and Tritrichomonas foetus) were entered into the indexed sources and with no limit was set for the year of publication. Among 374 studies imported for screening, 96 were duplicates, and 255 were excluded for irrelevancy as these studies did not meet the inclusion criteria (report original data, vaccine tests in cattle, and used either commercial or experimental vaccines that incorporated antigens from T. foetus). A further five studies were excluded after full-text review as either the publication described a different target pathogen or the full text was not in English. Eighteen studies met the inclusion criteria and were subjected to data extraction using the Covidence platform. Studies included in the systematic review reported three vaccine strategies, including subunit, cell fraction, and whole-cell killed vaccines. This review considers the design, rationale, and results of each of the 18 studies to provide a comprehensive overview of the current knowledge and to inform future research agendas. While whole-cell killed vaccines are most prevalent, they have shown superior efficacy compared to subunit vaccines studied to date. One study using a purified fractions of T. foetus cell membranes as vaccine demonstrated higher efficacy and higher calving rates compared to the whole-cell killed vaccine. All of these methods require cell culture growth of T. foetus which can be challenging compared to the production of recombinant proteins. At this stage, no T. foetus recombinant antigens have been reported. Advances in understanding the parasite's genome, pathogenesis, host-parasite interactions, and host immune responses to T. foetus will provide opportunities for the development of novel vaccine strategies for bovine trichomonosis.

Leishmania (Viannia) braziliensis causes cutaneous and mucocutaneous leishmaniasis. Macrophages are host cells for parasite replication and act as effector cells against the parasite. The two main macrophage phenotypes (M1 and M2) and their polarisation states have been implicated in Leishmania infection despite scarce data on L. (V.) braziliensis. In this study, we investigated the temporal and spatial distribution and predominance of M1 and M2 macrophages during L. (V.) braziliensis infection in Balb/c mice. Animals were infected with L. (V.) braziliensis promastigotes and were monitored for 25 weeks. Histopathological evaluation of footpad lesions, regional lymph nodes, and spleen; cellularity; and macrophage population quantification of M1, and M2 macrophages by flow cytometry were performed in different tissues. The results showed that after infection with either strain of L. (V.) braziliensis the lesions were small and non-ulcerated. The dissemination of parasites to tissues reinforced the characteristic visualisation of dermotropicL. (V.) braziliensis. The proportion of M2 macrophages in different tissues was significantly higher than that of M1 macrophages. Overall, the results reported here confirm that Leishmania an intracellular parasite, promotes and influences macrophage phenotype polarisation in different tissues over time, and researchers testing therapies based on macrophage phenotype regulation should consider this evidence.

The mechanistic study of new pharmaceutical compounds is crucial for evaluating their efficacy, identifying potential side effects, and optimising drug formulations. This study aimed to investigate the mechanism of action of trigonelline on the promastigote and amastigote stages of Leishmania major (MRHO/IR/75/ER). An initial in silico study was conducted to examine the pharmacological effects of trigonelline using molecular docking to evaluate the potential binding affinity of trigonelline with nitrate, a crucial molecule in the macrophage immune response against Leishmania. In this experimental study, the inhibitory mechanism of trigonelline on promastigotes was evaluated by measuring metacaspase expression levels. In the amastigote stage of L. major, the expression levels of inducible nitric oxide synthase (iNOS), interleukin 12 (IL-12), interferon-gamma (IFN-γ), tumour necrosis factor alpha (TNF-α), transforming growth factor-β (TGF-β) and interleukin 10 (IL-10) genes were assessed using Real-time PCR. Trigonelline demonstrated a high-binding affinity to the iNOS molecule in computer modelling. In macrophages treated with various concentrations of trigonelline, glucantime and their combination, the expression levels of metacaspase, IL-12, TNF-α, IFN-γ and iNOS genes significantly increased compared to the control group (p < 0.05), whereas IL-10 and TGF-β gene expression levels significantly decreased (p < 0.05). Trigonelline exerts its antileishmanial effects through its high antioxidant properties, non-cytotoxicity to macrophages, and its ability to enhance apoptosis and cell cycle arrest in promastigotes of L. major.

An 8-year-old boy developed serpiginous erythema on the soles of his feet and was diagnosed with cutaneous larva migrans (CLM). Following treatment with ivermectin, the erythema improved within 7 days, but it recurred 14 days later, requiring a second dose for complete resolution. Ultrasound and MRI did not reveal any parasites, but fluctuations in eosinophils, IgE and IgA levels were observed during treatment. This case highlights the importance of combining multiple diagnostic methods to evaluate treatment effectiveness.

Fasciola hepatica is a trematode parasite of significant veterinary and public health importance, causing economic losses in livestock due to liver damage, weight loss and reduced milk production. Although triclabendazole (TCZ) is available for treatment, it does not prevent the disease or reinfection. Infected animals exhibit strong immunoregulation, increasing susceptibility to secondary infections and altering vaccine-induced antibody responses. This study investigates the humoral immune response in cattle infected with F. hepatica at different stages of infection and evaluates the effect of TCZ treatment on this response. It also examines how fasciolosis affects the antibody response induced by bacterial vaccines during early and chronic infection stages. Experimental infections in steers were conducted, with faecal and plasma samples collected at various intervals. The results showed a decrease in parasite-specific antibody avidity during infection. However, F. hepatica infection did not substantially modify antibody response to bacterial vaccines. This study underscores the need for further research on the impact of fasciolosis and its treatment on livestock vaccination efficacy.

Gamma irradiation was applied to the tachyzoites Toxoplasma gondii virulent strain at doses of 0.25, 0.5, 1, 1.5 and 2 KGy. Radiation's effects were assessed both in vivo and in vitro. In vitro, the modest dosage of radiation, 0.25 KGy, showed 97% tachyzoites viability with only slight surface abnormalities and a normal crescent form using a scanning electron microscope. Protein analysis by SDS-PAGE demonstrated that while higher doses of radiation altered the protein banding profile, the 0.25 KGy irradiated tachyzoites showed no significant changes compared to the control (non-irradiated tachyzoites). While, tachyzoites exposed to the higher dose of irradiation (1, 1.5 and 2 KGy) resulted in the appearance of a new protein band as the molecular weights detected were 60, 30 and 10 kDa for antigens prepared from tachyzoites exposed to 1 kDa, and 1.5 and 60, 28 kDa for antigen prepared from tachyzoites exposed to 2 KGy. The immunogenicity of the tachyzoites exposed to radiation did not reveal any significant change in comparison with no irradiated tachyzoites when tested by ELISA using sheep-infected sera. A study conducted in vivo evaluated the infectivity of irradiation tachyzoites by inoculating mice with a 2500 tachyzoites virulent strain/mouse. There are six groups of mice, each with twelve animals, for the six doses of radiation. Mice harbouring irradiation tachyzoites remained viable until 40 days post-inoculation. On the other hand, the mice of control group had a mean survival time of 6.5 ± 0.22 days, and none of them survived past 7 dpi. Comparing the attenuated T. gondii tachyzoites at 0.25 KGy to the control group and other groups injected with irradiated tachyzoites, the results showed statistically significant increases in total IgG. Compared to other irradiation groups, the group injected with 0.25 KGy irradiated tachyzoites had a considerably higher level of IFN γ and IL17 (p < 0.000001). The groups which received 0.25 and 0.5 KGy irradiated tachyzoites as an injection showed no discernible variation in their higher levels of IL12. The findings imply that gamma irradiation was successful in reducing the pathogenicity of the T. gondii virulent strain while preserving the potential of the irradiated tachyzoites to induce an immunological reaction. An investigation into this immune response's immunoprotective potential is advised.

Gastrointestinal helminths interact with the gut microbiota in ways that shape microbiota structure and function, but these effects are highly inconsistent across studies. One factor that may help explain variation in parasite-microbiota interactions is host sex since helminths can induce sex-specific changes in feeding behaviour and diet that might cascade to shape gut microbial communities. We tested this idea using an anthelmintic treatment experiment in wild Grant's gazelles (Nanger granti). We found that in males, anthelmintic treatment induced short-term shifts in microbial diversity and structure within ~40-70 days, but in females, treatment had effects on microbiota structure that emerged over a longer period of ~500 days. Long-term effects of treatment on the microbiota of females were potentially due to sex-specific changes in feeding behaviour since deworming nearly doubled the time females spent feeding, but did not affect feeding time in males. In support of this idea, anthelmintic treatment eliminated associations between microbial diversity and diet in females, and treated females maintained a more stable abundance of microbial taxa and predicted functions. Together, these findings suggest that accounting for host traits can help uncover mechanisms, such as changes in diet, by which helminths interact with the microbiota.

Trypanosome parasites of the genus Trypanosoma cause African animal trypanosomosis, a devastating livestock disease plaguing sub-Saharan Africa. Unlike many protozoan parasites, these extracellular blood-borne pathogens directly engage the host's immune system. While the mouse model has provided valuable insights, a comprehensive understanding of the bovine immune response to trypanosomes remains elusive. Addressing the immune response in cattle, the most relevant host species, and how it takes part in mitigating the negative impact of the disease could contribute to setting up sustainable control strategies. This review summarises the current knowledge of the immune response in cattle during trypanosomosis. Following a brief overview of infection processes and bovine trypanotolerance, we present advances in the regulation of host innate, inflammatory and adaptive responses and delve into the key immunological players involved in immunoactivities and immunosuppression. We discuss how these mechanisms contribute to tolerance or susceptibility to infection, highlighting critical gaps in knowledge that require further investigation.

Fasciolosis is a parasitosis of great importance for livestock, as well as for public health, as it is considered by the WHO as a neglected disease. Disease control is complex and reinfections make the use of therapeutic products an unsustainable method from an economic, environmental and health point of view. The aim of this study was to evaluate a new vaccine formulation for dairy cattle, containing soluble Fasciola hepatica antigens associated with Montanide 763 AVG and saponin adjuvants (FhSAMS). The vaccine was tested with two protocols, a single dose and a booster dose 6 months after the first dose. The FhSAMS vaccine proved to be safe, with no side effects. Furthermore, it was able to generate a more robust humoral immune response when a six-month booster dose was used, in addition to stimulating greater production of IFN-ʏ, indicating a Th1 profile immune stimulus.

Toxoplasma gondii infection has been associated with psychoneurological disease in humans and behavioural changes in rodents. However, the mechanisms accounting for this have not been fully described and in some cases could be argued to reflect the severe neuropathology that some mice suffer during infection. Herein we employ a multi-omics approach to extensively examine BALB/c mice that are resistant to toxoplasmic encephalitis. Using a combination of LCMS (liquid chromatography-mass spectrometry) and RNAseq we demonstrate that infection alters the neurochemistry and the transcriptome of the brains of BALB/c mice. Notable changes to tryptophan, purine, arginine, nicotinamide and carnitine metabolism were observed in infected mice and this was accompanied with changes to the levels of a number of transcripts associated with enzymes these metabolic pathways. In addition, changes were seen in transcripts of many immunologically important genes known to contribute to immunity to T. gondii. Changes in the levels of additional transcripts during infection have previously been associated with psychoneurological diseases. The results demonstrate that the BALB/c mouse, with its relatively mild neurological disease, is a useful model for characterising the effects of T. gondii infection on murine neurochemistry. The results also implicate specific biochemical pathways in mediating these changes and should inform further mechanistic studies and suggest therapeutic targets.

For decades, parasitic worms such as Trichuris muris have been maintained in laboratory animals, providing insights into host-parasite interactions and host immune responses. The most used T. muris isolate is the E isolate, established in the laboratory in 1954. However, one concern with these model systems is the potential for laboratory-induced selection and therefore changes in host-parasite interactions. To address these concerns, we compare the E isolate with a recently isolated T. muris isolate (M isolate), established from wild house mice (Mus musculus domesticus, Isle of May, UK), in their capacity to infect laboratory mice. High dose infection of C57BL/6 mice revealed that significantly more parasites of the M isolate survived to the adult stage compared to the E isolate. Worm persistence was associated with heightened TNF-α and IL-10 secretion upon parasite-specific re-stimulation, and higher serum IgG1 and IgG2c levels, concomitant with an increase in T-bet and ICOS CD4 T effector-memory cells. Differences in host response to the isolates were not as pronounced during low dose infection. Our study highlights the need for regular evaluation of lab-maintained parasite isolates against freshly isolated parasites to understand whether the established lab strains remain relevant model systems for our understanding of parasitic infections.

Schistosomiasis causes severe hepatic fibrosis, making it a global health issue. Moringa oleifera seed oil extract, which had antiparasitic, anti-inflammatory and antioxidant effects, was investigated as an alternative treatment. The 50 mice were divided into control, infected, praziquantel-treated, M. oleifera seed oil extract-treated and combined treatment groups. These treatments were examined for their effects on egg granulomas, hepatic enzymes, total protein, albumin, antioxidant enzymes and pro-inflammatory cytokines. M. oleifera seed oil and/or PZQ significantly reduced egg numbers, granuloma size and liver histopathology. M. oleifera seed oil reduced hepatic enzyme activity, increased total protein and albumin, and increased antioxidant enzyme activity while decreasing malondialdehyde. M. oleifera seed oil reduced the levels of pro-inflammatory cytokines. M. oleifera seed oil may treat schistosomiasis instead of PZQ due to its antifibrotic, immunomodulatory and schistosomicidal properties.

Interleukin 27 (IL-27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL-27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL-27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL-21, anti-L. infantum antibodies and parasite loads. We performed functional assays followed by IL-27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD-1, CTLA-4, phospho-Stat-1/3, T-bet, GATA3 and nitric oxide production (NO). Both IL-27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL-21 (r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti-L. infantum IgG antibodies (r = 0.38, p < 0.040) and parasite load (r = 0.47, p < 0.009). IL-27 and IL-21 participate of immune responses in CanL. IL-27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD-1, CTLA-4, T-bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL-27 are involved in CanL pathogenesis in the host, and may be targets for new therapies.

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC of 0.00494 ± 0.00095 mg/mL for promastigotes and EC of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.

Leishmaniasis is considered one of the most critical health concerns in the world. Unfortunately, no protective vaccines exist and conventional treatments are relatively ineffective. Therefore, new strategies are necessary against leishmaniasis. In recent years, exosomes have shown promising therapeutic outcomes in various diseases, including infectious diseases. In this regard, we aimed to explore the effect of the exosome, pyrimethamine and their combination on the anti-parasitic function of RAW264.7 cells against Leishmania major. Exosomes were isolated from the C57BL/6 peritoneal macrophages. L. major infected and non-infected RAW264.7 cells treated with exosomes, pyrimethamine (PM), and exosomes along with PM. The effect of the treatments was analysed on phagocytosis, efferocytosis, the intracellular parasite count, arginase activity, nitric oxide (NO) and reactive oxygen species (ROS) production. Exosomes could significantly elevate the phagocytosis, efferocytosis, NO and ROS in both infected and non-infected groups (Pv < 0.05). The exosomes reduced the arginase activity in both groups (Pv < 0.05). The intracellular parasite count was significantly lower after treatment with exosomes (Pv < 0.05). These results demonstrate that MQ-derived exosomes can enhance in vitro anti-parasitic responses against L. major. This provides a potential pathway for more effective treatments and underscores the importance of further research in this area.

Vaccine efficacy varies globally, often showing reduced immune responses in low- and middle-income countries, possibly due to the immunomodulatory effects of parasitic infections like malaria. This systematic review evaluates the impact of malaria on immune responses to unrelated vaccines in humans and animals. We systematically searched five databases-MEDLINE, Web of Science, Global Health, Scopus and Embase-up to 5th December 2023. Eligible studies compared immune responses to WHO-approved vaccines between malaria-infected and uninfected groups, or between antimalarial-treated and untreated groups. Meta-analysis was performed using random-effects models with standardised mean differences (SMDs) as summary statistics. The study is registered with PROSPERO (CRD42022298053). Twenty-four articles (17 human, 7 animal) met the inclusion criteria, with 13 human articles contributing data for the meta-analysis. Significant heterogeneity was observed. Vaccine responses were higher in malaria uninfected individuals (SMD 0.34, 95% CI 0.07 to 0.60, I = 87.15%) with weaker differences between antimalarial-treated and untreated groups (SMD 0.07, 95% CI -0.01 to 0.16, I = 85.01%). The overall SMD for malaria uninfected/treated vs. infected/untreated was 0.15, 95% CI 0.05-0.26, I = 90.91. Narrative analysis suggested malaria's adverse impact on vaccine responses in animals. Malaria infection may impair vaccines responses; with preventive treatment of malaria partially reversing these effects, highlighting the need for targeted public health interventions.

Leishmaniasis is a neglected tropical disease, caused by protozoan parasites of Leishmania (L.), and is transmitted by bite of phlebotomine sandflies. There are several studies on central nervous system infection to indicate that Leishmania can cross the blood-brain barrier, resulting in neurological manifestations, known as "cerebral leishmaniasis." This study highlighted the notions: (i) polarisation of bone marrow-derived macrophages (BMDM) incubated following stimulation with lipopolysaccharide (LPS) or soluble Leishmania antigen (SLA), (ii) quantification of parasites within co-culture of Leishmania-infected macrophages, and astrocytes, and (iii) effect of interferon-gamma (IFN-γ) on the infection rate of co-culture populations. Accordingly, 83% of overall macrophage population was identified on day 7 for CD11b and F4/80 macrophage markers. Flow cytometry analysis revealed significant increases in CD11b and F4/80 surface markers in LPS and SLA-stimulated BMDMs at 24 h, compared to untreated cells. TNF-α levels increased significantly in both LPS and SLA-treated BMDMs after 48 h. Additionally, SLA treatment induced a more elongated, spindle-like shape in the cells, indicative of M2 macrophage polarisation over the M1 phenotype. When non-infected astrocytes with/without stimulation with IFN-γ before co-culture, gp63 FITC-labelled parasite populations (%) in co-culture decreased to 25% at 72 h, thus indicating a lower infection rate in a time-dependent manner. IFN-γ and IL-6 levels significantly increased to 71.66 ± 3.51 and 184 ± 14.42 pg/mL, resulting in the inflammatory response in the co-culture system at 48 h (p ≤ 0.0001), when compared to the control (30 ± 2.52 pg/mL for IFN-γ and 8.66 ± 2.37 pg/mL for IL-6) at 0 h of the incubation. It is the first study to emphasize the communication between Leishmania-infected macrophages and astrocytes regarding Leishmania parasite load. The results suggest that astrocytes can lead to the reduction in Leishmania parasites, thereby controlling the incidence of cerebral leishmaniasis.

Obligate intracellular protozoan parasite, Leishmania donovani, causative agent of visceral leishmaniasis, led to impaired macrophage functions. It is well documented that many of these changes were induced by parasite-mediated reduction in macrophage cholesterol content. Leishmania-mediated alteration in the other lipids has not been explored in detail yet. Here, we found that the expression of key cholesterol biosynthetic genes and total cellular cholesterol were reduced during L. donovani infection. Further, we have also identified that this reduction in the cholesterol led to increased membrane fluidity and inhibition of antigen-presenting potential of macrophages. In addition to this, we studied the relative changes in different lipids in THP-1-derived macrophages during L. donovani infection through liquid chromatography-mass spectrometry. We found that Sphingomyelin (16:0) and ceramide (20:1, 26:0 and 26:1) were significantly reduced in infected macrophages. We further observed that the majority of different sub-classes of phospholipids were downregulated significantly. Overall ratio of phosphatidylcholine versus phosphotidylethanolamine was decreased which indicated the compensatory mechanism of cell in response to cholesterol reduction. The observed Leishmania-mediated alteration in macrophage-lipidome provided the novel insights into mechanism of host-pathogen interactions.

The major histocompatibility complex (MHC) molecules play an integral role in the adaptive immune response to transmissible cancers through tumour antigen presentation and recognition of allogeneic MHC molecules. The transmissible devil facial tumours 1 and 2 (DFT1 and DFT2) modulate MHC-I antigen presentation to evade host immune responses and facilitate transmission of tumours cells to new Tasmanian devil (Sarcophilus harrisii) hosts. To enhance T-cell-driven tumour immunogenicity for vaccination and immunotherapy, DFT1 and DFT2 cells were co-transfected with (i) NLRC5 for MHC-I expression or CIITA for MHC-I and MHC-II expression, and (ii) a co-stimulatory molecule, either CD80, CD86 or 41BBL. The co-transfected DFT cells presented enhanced expression of MHC-I and/or MHC-II. As few devil-specific monoclonal antibodies exist, we used recombinant CTLA4 and 41BB fused to a fluorescent protein to confirm expression of cell surface CD80, CD86 and 41BBL. The capacity for these cells to induce T-cell responses including PD1 and IFNG expression was evaluated in in vitro co-culture assays with captive devil peripheral blood mononuclear cells (PBMCs). Although PBMC viability had increased, there was no evidence of enhanced T-cell activation. This system can be used to identify additional factors required to promote activation of naïve devil T-cells in vitro.

Hepatic ischaemia-reperfusion (I/R) injury is a frequent and nearly inevitable pathophysiological process without widely accepted effective therapy. Soluble egg antigen (SEA) of Schistosoma japonicum (S. japonicum) is the main mediators capable of regulating immunological activities and has received increased attention in immune-mediated diseases. But its role in hepatic I/R injury has not been well defined. This study aimed to elucidate whether SEA protects liver against hepatic I/R injury and explore underlying mechanism. After intraperitoneal injecting SEA three times a week for 4 weeks, mice underwent 70% hepatic I/R injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), haematoxylin-eosin (HE) and TdT-mediated dUTP nick-end labelling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response was also investigated. Furthermore, immunofluorescence was used to detect macrophage polarisation. Compared with the hepatic I/R injury group, SEA pretreatment significantly alleviated hepatic I/R injury induced liver damage, apoptosis and inflammatory. Interestingly, SEA enhanced the polarisation of macrophages towards M2 macrophages in vivo. We are the first to investigate the therapeutic efficacy of S. japonicum SEA in a hepatic I/R injury model in mice. We provided the first direct evidence that SEA attenuated hepatic I/R injury by promoting M2 macrophage polarisation.