Parasite Immunology最新文献

This study aimed to elucidate how osteopontin (OPN) affects the growth, invasion, and extrahepatic metastasis of Echinococcus multilocularis (Em) through the p38MAPK signalling pathway of host hepatocytes. C57BL/6J mice were randomly divided into the control group (n = 10), the LV-OPN-0423 group (n = 10), the anti-p38MAPK group (n = 10), and the anti-p38MAPK + LV-OPN-0423 group (n = 10). Em infection models in mice were set up. The mice were fed for 6 weeks under suitable conditions. The mice in the anti-p38MAPK group and the anti-p38MAPK + LV-OPN-0423 group were then given SB202190 (this is an inhibitor of p38MAPK) for 4 weeks, and the mice in each group were injected with corresponding lentivirus diluent once a week for 8 weeks. After the intervention was completed, the liver volume and weight were measured, and the liver was embedded in paraffin and sectioned. Sections were subjected to haematoxylin and eosin (HE), periodic acid-Schiff (PAS), and immunohistochemical staining to observe the growth and invasion of Em, as well as the expression levels of OPN, p38MAPK, and p-p38MAPK of the host. SB202190 hindered Em's growth, invasion, and migration. The level of OPN facilitated Em's growth, invasion, and migration, which can be reversed by SB202190. The OPN level promoted the expression of p38MAPK and p-p38MAPK. These results suggested that OPN could regulate Em's growth and metastasis through the p38MAPK signalling pathway in host hepatocytes, providing evidence that OPN and p38MAPK may be novel molecular targets for treating alveolar echinococcosis.

Lymphatic filariasis results in chronic edema, pain, elephantiasis and disfigurement in humans. It was previously reported that platelet aggregation is inhibited in lymphatic filariasis patients, compared to healthy controls. However, it was not clear whether the inhibition was due to filarial parasite infection or due to the presence of edema. This study was planned to compare platelet functions, plasma proteins and lipids in filarial and non-filarial edema patients. Edema patients were tested for the presence of filarial antigens and antibodies in their blood and were grouped as filarial and non-filarial edema patients accordingly. Platelet aggregation, size distribution, platelet activation markers, plasma proteins and lipids were measured in collected blood samples. Results showed that platelet aggregation was significantly inhibited in filarial edema patients, compared to non-filarial edema patients. Soluble P-selectin and beta thromboglobulin showed significant positive correlation with each other only in non-filarial edema patients. Plasma total cholesterol was lower in filarial edema patients, and HDL was lower in only female filarial edema patients. Observations confirm that inhibition of platelet functions is due to filarial parasite infection, not merely due to the presence of edema. Results also indicate uncoupling and disturbances of platelet activation processes.

Ocular toxoplasmosis (OT) is a common cause of posterior uveitis worldwide, primarily caused by Toxoplasma gondii. The immune response plays a crucial role in OT pathogenesis. However, a study using aqueous humour samples has limited applicability due to the invasive procedure. This study used peripheral blood samples to compare the concentrations and ratios of cytokines involved in Th1, Th17 and Treg immune responses between OT patients and seropositive individuals without ocular lesions (SP) who met the inclusion criteria. The ELISA method was used to measure cytokine concentrations, and the cytokine ratio was determined by comparing the concentration of two cytokines. This study revealed the differences in the concentrations of IL-17 (p = 0.015), IFN-α (p = 0.015) and IL-6 (p = < 0.001) between OT and SP groups, as well as the ratio of IFN-α/TGF-β (p = 0.012), IFN-β/TGF-β (p = 0.020), IL-17/TGF-β (p = 0.018), TNF-α/TGF-β (p = 0.015), IL-17/IL-6 (p = 0.003), IL-6/IFN-γ (p = < 0.001) and IL-6/TNF-α (p = < 0.001). Among the variables, the IFN-α concentrations and IL-6/TNF-α ratio were the most significant factors influencing the risk of OT. The novel findings of this study regarding the involvement of IFN-α in the pathogenesis of OT are considered important and have the potential to reveal a predictive factor for the occurrence of OT in humans.

Toxoplasma gondii is a protozoan parasite causing Toxoplasmosis in humans. Interleukin-6 (IL-6) is a multifunctional cytokine that controls infection and helps maintain pregnancy. The study investigated the impact of IL-6 promoter polymorphism on blood IL-6 levels and pregnancy outcomes in T. gondii-infected women. A cross-sectional study was conducted on 244 women, including 83 infected in Group 1 (Group 1a = 43, Group 1b = 40), 81 uninfected with RPL (Group 2), and 80 controls (Group 3). Blood and placental tissue samples were collected, and screened for IL-6 levels using ELISA. The DNA was isolated, amplified for T. gondii DNA and the IL-6 gene by PCR, and the IL-6 gene was sequenced using the Sanger method. The genotypic (p < 0.001) and allelic (p < 0.001) frequencies were significantly variable. Highly prevalent genotypes were A10T11/A10T11 in Group 1a (28%), A9T11/A9T11 in Group 1b (27.5%) and Group 2 (33.3%), while A8T12/A10T10 and A10T10/A10T10 were in Group 3 (20% each). The mean blood IL-6 levels were significantly variable in all the study groups (p < 0.0001). The A9T11/A9T11 genotype was significantly linked with high IL-6 levels, while the A10T10/A10T11, A10T11/A10T11 and A10T10/A10T10 genotypes were associated with low IL-6 levels. In conclusion IL-6 AnTn polymorphism is associated with changed IL-6 levels and RPL in women infected by T. gondii.

As an effort towards vaccine development against African trypanosomiasis, we studied key parasite molecules that mediate VSG functions, specifically the major surface protease-B of Trypanosoma brucei that catalyses proteolytic removal of old VSGs for expression of new ones, an important stage-specific function that allows the parasite to survive in its host, thus making it an attractive candidate for vaccine development. Herein, the Tbmsp-b gene was cloned into a pVAX-1 plasmid to produce the pVAX-1-Tbmsp-b construct for DNA vaccine trials. BALB/c mice were immunised by intradermal injection with a 100 μg dose of the construct thrice on Days 0, 21 and 42, then inoculated with 2000 parasites on Day 56. Anti-trypanosome-specific antibody (IgG) and cytokine (IFN-γ) were monitored by ELISA from sera of immunised and unimmunised mice. Immunised mice showed significantly (p < 0.05) higher IgG and IFN-γ responses, lower parasitaemia (by 75% and 51.2% of parasitaemic scores on the first and fifth week of infection) and longevity by up to 22 days compared to unimmunised mice. These results showed that the construct provided partial protection to virulent T. b. brucei (Federe strain) infection in susceptible BALB/c mice, suggesting the potential for using MSP-B as an antigen in DNA vaccine development against African trypanosomiasis.

Human babesiosis is an emerging infectious disease caused by a bloodborne single-celled parasite belonging to the genus Babesia. Cases of human babesiosis are commonly reported in the United States, Western Europe and Asia. In the United States, the two major causative agents are Babesia microti and Babesia duncani. Transmitted to humans through tick bites, the parasite infects host red blood cells (RBCs). It induces flu-like symptoms and has evolved mechanisms to manipulate the immune system, enabling its persistence. One key mechanism is the secretion of extracellular vesicles (EVs) which carry bioactive molecules, including proteins, lipids and genetic material that modulate pathogen-host interactions and disease development. The inhibition of the secretion of these vesicles may lead to disease control. One potential inhibitor of extracellular vesicle secretion is linoleic acid (LA), a polyunsaturated lipid that has demonstrated inhibitory properties in other parasites. To study the effects of development stage-dependent stimuli on B. duncani, we employed a B. duncani in vitro continuous culture system and evaluated the use of sorbitol for synchronising parasite development. Microscopy techniques showed successful sorbitol-induced synchronisation. Using nanoparticle tracking analysis and scanning electron microscopy, we assessed the effects of LA on parasite morphology and EV characteristics. Our studies indicate that exposure of Babesia parasites to LA did not cause significant observable changes in RBC morphology or reduce EV concentrations under the tested conditions.

Cancer is one of the main causes of morbidity and mortality worldwide. Toxoplasma gondii (T. gondii) infection and antigens can be used to exert valuable antitumor effects. We studied the effect of Toxoplasma lysate antigen and excretory/secretory antigens (ESAs) produced by T. gondii tachyzoites on Ehrlich solid carcinoma (ESC)-bearing mice by histopathology (H&E), immunohistochemistry (iNOS, VEGF, caspase 3), immunological (IFN-γ and specific anti-T. gondii IgG) and biochemical studies (redox state markers; MDA and SOD as well as apoptotic markers; BAX and BCL2). The results showed strong anti-murine ESC effect by increasing tumour necrosis and apoptosis (high caspase 3 and BAX with low BCL2) as well as decreasing angiogenesis (weak VEGF and iNOS) and by increasing oxidative stress (low SOD with high MDA). In addition, specific anti-T. gondii IgG was confirmed and high IFN-γ was detected. We concluded that ESAs could be used as an effective supplementary biotherapy in the treatment of cancer.

This study investigated whether miRNAs and cytokines could be markers of gestational and/or congenital toxoplasmosis (TX). A total of 172 clinical samples collected from women were investigated. For gestational TX, 63 plasmas from pregnant women were analysed: 44 with gestational TX (GT-PW), 11 with asymptomatic TX (AsT-PW) and 8 healthy pregnant women (H-PW). For controls, 68 plasmas: 34 healthy women (HW) and 34 with asymptomatic TX (AsT). For congenital TX, 41 amniotic fluid (AF) samples were tested: 29 with negative qPCR in AF and 12 with positive PCR. Nine miRNAs were assayed by qPCR in plasma and AF samples. IFN-γ, TNF-α and IL-10 detection in plasmas was performed by ELISA. Statistical analyses were determined by F-test and ROC curves. Among the 9 hsa-miRNAs studied, only hsa-miR-125b-5p was significantly expressed in the AsT-PW group. hsa-miR-144-3p was more expressed in the GT-PW group. In AF samples, hsa-miR-125b-5p was more expressed in 29 AF samples with Neg-qPCR and hsa-miR-144-3p in AF samples with Pos-qPCR. Pregnant women from the GT-PW group had lower IFN-γ, TNF-α, and IL-10 production than the other groups. The in silico analyses identified pathways for hsa-miR-144-3p and hsa-miR-125b-5p and were related to the pathogenesis and immune response in toxoplasmosis. These findings suggest that hsa-miR-125b-5p could be related to infection regulation and to be characterised as a potential marker for asymptomatic toxoplasmosis. On the other hand, the hsa-miR-144-3p could be related to the exacerbation of the infection since gestational and/or congenital TX groups expressed high expression of hsa-miR-144-3p and low expression of IFN-γ, TNF-α and IL-10.

Toxoplasma gondii is a parasitic protozoan that infects nucleated cells and poses a major threat to human and animal health. Developing effective vaccines is critical for controlling toxoplasmosis. Immune Mapped Protein 1 (IMP1) is a protective antigen located on the plasma membrane of T. gondii. This study aimed to evaluate the efficacy of IMP1 as a DNA vaccine, either alone or combined with IL-12 as an adjuvant, in BALB/c mice. The use of IL-12 as an adjuvant was based on its well-documented ability to enhance Th1 immune responses in DNA vaccines against T. gondii. Mice were divided into five groups: group I served as a control (100 μL PBS), group II received empty pcDNA3.1, group III received pcIL12, group IV received pcTgIMP1, and group V received a combination of pcTgIMP1 and pcIL12 (50 μg each). Immunisation was administered three times on days zero, 14, and 28 with the same dose. Two weeks post-final vaccination, mice from each group were either challenged with a lethal dose of T. gondii for survival monitoring or euthanised for evaluating immune responses, including antibody levels, lymphocyte proliferation, and cytokine production. Results showed that mice immunised with pcIMP1 + pcIL-12 or pcTgIMP1 alone exhibited robust immune responses against Toxoplasmosis. These responses included elevated levels of IgG1 and IgG2a antibodies, a strong lymphoproliferative response, and higher levels of IFN-γ and IL-4 production compared to the other groups. Furthermore, mice immunised with pcIMP1 + pcIL-12 demonstrated prolonged survival times compared to the empty pcDNA3.1, pcIL-12 alone, and control groups (p < 0.05). Our finding underscores the potential of IMP1 as a vaccine candidate and highlights the adjuvant effect of IL-12 in enhancing protective immunity against toxoplasmosis.

Patients undergoing haemodialysis are known to have compromised immune function, which can increase their susceptibility to infections, including intestinal parasitic diseases. These infections can manifest more severely in this population. Typically, the immune response to parasitic infections involves a shift from a Th1-dominant response-more effective against intracellular pathogens-to a Th2-dominant response, which promotes eosinophilia and IgE production. Participants were categorised into eosinophilic and non-eosinophilic groups based on eosinophil counts (< 10 cells/mL). T-bet and GATA-3 gene expressions were quantified using SYBR Green real-time PCR. The overall prevalence of intestinal parasitic infections was 11.9%, including Blastocystis hominis (5.9%), Endolimax nana (3.7%), Entamoeba coli (1.5%), and Giardia lamblia (0.7%). A significant association was found between parasitic infections and eosinophilia (p = 0.01). No significant difference in IgE levels was observed between the two groups. GATA-3 expression was significantly higher in eosinophilic patients compared to non-eosinophilic ones within the 90% confidence interval. A negative correlation was identified between eosinophil count and GATA-3 expression (r = -0.37, p = 0.05). Haemodialysis patients exhibit disruptions in both humoral and cellular immune responses. Further research is necessary to elucidate the role of eosinophilia and Th1/Th2 balance biomarkers in the diagnosis and prognosis of mortality risk among this population.