Parasite Immunology最新文献

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.

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.

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.

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.

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.

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.

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.

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.

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.