Parasite Immunology最新文献

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.

American tegumentary leishmaniasis (ATL) affects the skin and mucous membranes, with a spectrum shaped by Th1/Th2 responses. This study investigated inflammasome activation in correlation with macrophage subpopulations, tissue parasitism, and histological changes in cutaneous and mucocutaneous leishmaniasis. We assessed inflammasome activation, tissue parasitism, and macrophage populations by immunohistochemistry, correlating with histopathological alterations using 29 biopsies from cutaneous and mucocutaneous leishmaniasis. Cutaneous leishmaniasis showed higher parasite density and infected macrophages than mucocutaneous leishmaniasis skin and mucosal lesions (p < 0.05). CD68⁺ and CD163⁺ macrophages were more abundant in cutaneous leishmaniasis (p < 0.0001 and p < 0.05). Inflammasome markers IL-1β⁺ and IL-18⁺ were significantly higher in cutaneous leishmaniasis (p < 0.05). In cutaneous leishmaniasis, CD68⁺ macrophages correlated positively with inflammasome markers, whereas in mucocutaneous leishmaniasis, CD163⁺ cells showed strong negative correlations with IL-1β and caspase-1. Parasite density correlated positively with inflammasome activation in cutaneous leishmaniasis but negatively in mucocutaneous leishmaniasis. Findings suggest that inflammasome activation plays different roles in ATL. In cutaneous leishmaniasis, inflammasomes contribute to the inflammatory response and parasite clearance, while in mucocutaneous leishmaniasis, they are less relevant, possibly due to a more defined immune response with minimal parasitism.

Trypanothione reductase (TryR) is a unique and key redox protein of Leishmania donovani, the causative agent of visceral Leishmaniasis. In this work, we have developed a promising multiepitope vaccine using TryR. Multiple epitopes from TryR were identified using different bioinformatics tools to stimulate both humoral and cellular immune responses. An adjuvant was also included to enhance the antigen presentation and immune activation. Using bioinformatics tools, immunodominant T-cell and B-cell epitopes of TryR were predicted, and based on the findings, a chimeric multi-epitope vaccine construct was designed. The structural stability of the final construct was validated using different bioinformatics tools. Furthermore, a docking study was conducted with the human TLR4 receptor to assess the affinity of the multi-epitope construct. The Ramachandran plot analysis, Z score, and ERRAT support the stability of the multi-epitope vaccine candidate. Furthermore, in silico analysis showed that the multi-epitope vaccine candidate has high affinity with the human TLR4 receptor and has broad efficacy based on the population coverage. Immune stimulation confirmed the pro-inflammatory response with T- and B-cell activation.

Naegleria fowleri is the etiological agent of primary amoebic meningoencephalitis (PAM), a lethal disease with a 97% mortality rate in humans. Currently, there is no vaccine that confers protection against N. fowleri. Recently, we reported that the synthetic membrane peptide (Smp145) was considered as a vaccine candidate, since it induced 60% protection in mice immunised and challenged with N. fowleri. The objective was to design in silico a vaccine based on the A1 domain of cholera toxin (CT), coupled to the Smp145 peptide of N. fowleri, and to evaluate its protective effect in a murine model of PAM. A bioinformatic design was performed with the Ser61Phe mutation in the active site of the A1 domain of CT (mCTA1), linked through a glycine linker to Smp145. Intraperitoneal immunisation with mCTA1-Smp145, followed by challenge with a lethal dose of N. fowleri, resulted in 60% protection, confirming its protective capacity as the most relevant finding. Furthermore, increased levels of IgA and IgG were observed in sera and nasal washes, which recognised antigenic bands of mCTA1-Smp145 and total extracts of N. fowleri. Overall, we propose mCTA1-Smp145 as a potential vaccine against N. fowleri, highlighting that its protective effect constitutes the main support for this proposal.

Schistosome parasites are known to modulate host immune responses, which is achieved in part through the release of excretory/secretory (ES) products, including extracellular vesicles (EVs). During chronic schistosomiasis, increased regulatory responses are found, which include enhanced IL-10 production by B (Breg) cells. ES products from schistosome eggs are able to induce IL-10 production by B cells. However, since infection with male worms only (without egg production) also promotes IL-10 producing B cells, we here studied the stimulatory effects of adult worm ES and EVs on murine and human B cells. Worm ES increased IL-10 release by mouse splenic B cells; this activity was concentrated in defined size-separated fractions of adult worm ES. Interestingly, mass spectrometry of the fractions that induced the highest IL-10 response revealed an enrichment of EV-associated proteins. Indeed, highly purified adult worm EVs could interact with mouse splenic B cells, visualised by binding of a schistosome-specific tetraspanin (TSP2) targeting antibody. Furthermore, purified adult worm EVs induced IL-10 release in both mouse splenic and human peripheral blood B cells, suggesting that adult worm EVs can play a role in immune regulatory processes within their host.

Leishmania parasite adeptly evades the host's immune defences by infiltrating macrophages, exploiting apoptotic processes for further dissemination. Among the host's strategies to counter parasitic propagation, the pivotal role of B-cells, specifically B regulatory (Breg) cells, emerges. Recent evidence from in vitro and in vivo studies has thrust Breg cells into the spotlight, attributed to their IL-10 secretion and antigen presentation. The escalated IL-10 production coupled with decreased Th1 response provides a conducive milieu for parasitic proliferation within host cells. This abundance of IL-10, from Breg cells and other immune sources, impedes T cell differentiation into Th1, Th2 and Th17 subsets. Moreover, IL-10 obstructs CD8+ T cell differentiation into cytotoxic T cells, heightening the host's susceptibility to infections. Breg cells are also implicated in the production of IL-35, which in turn mediates the conversion of B cells into Breg and IL-35+ Breg cells and helps Leishmania to evade the immune response. Notably, recent data underscore the potential of B cell reprogramming via BTK and MEK inhibitors, offering a novel immunomodulation strategy. This approach presents a novel avenue for curbing Breg cells, potentially hindering prolonged BCR signalling. Although promising for Leishmania infection immunotherapy, a comprehensive understanding of IL-10-producing B cells' exact role demands further exploration. Developing targeted strategies to modulate Breg cell function could revolutionise Leishmania treatment, enhancing patient outcomes. Understanding Breg cells' role offers promising avenues for precise immunotherapy against this challenging infection.

Interleukins 33, 25, and thymic stromal lymphopoietin (TSLP) are core components of type two immune responses and have been studied extensively using helminth infection models. However, many questions remain regarding their cellular sources, their immune recipients, as well as how they shape immunity. Recent literature has demonstrated non-epithelial alarmin production, acting primarily on lymphoid effector cells, and has suggested a role for alarmins in licensing of effector function in tissues during immunity, in dissent with conceptions of classical alarmins as epithelium-derived, myeloid-targeting, and induced prior to adaptive responses. This review examines recent findings in alarmin helminth interactions at barrier sites and discusses the wider implications for how alarmin responses are conceptualised.