Parasite Immunology最新文献

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.

Chagas disease, caused by Trypanosoma cruzi, exhibits a wide clinical spectrum, which is influenced by the parasite's extensive genetic diversity. Growing evidence indicates that human infections are often multiclonal, involving a dynamic population of parasite clones, collectively termed the "cruziome". The immunological consequences of these mixed infections, particularly at the initial host-parasite interface, remain poorly characterised. This study aimed to investigate how single versus co-infection with phylogenetically distinct T. cruzi strains modulates the innate immune response of murine macrophages. RAW 264.7 macrophages were infected with T. cruzi strains from Discrete Typing Unit (DTU) I (G strain) or DTU II (Y strain), either individually or in combination (co-infection). Assays for cellular invasion and intracellular multiplication were performed. The production of key cytokines (IL-1β, IL-18, IL-6, IL-10, IL-12) and nitric oxide (NO) was quantified at 24 to 96 h post-infection. The Y strain displayed significantly higher invasion and replication rates and induced a potent pro-inflammatory response, characterised by elevated levels of IL-1β, IL-18, IL-12, and NO. The G strain elicited a more regulatory profile, with a progressive increase in IL-10 production at later time points and lower levels of inflammatory mediators. Co-infection resulted in a distinct, hybrid immune profile, marked by intermediate levels of both pro-inflammatory and regulatory cytokines and a moderated NO output. Co-infection with phylogenetically distinct T. cruzi strains generates a unique immunomodulatory environment that is not merely an additive effect of the individual strains. These findings provide in vitro evidence supporting the hypothesis that the composition of the infecting parasite population shapes the host immune response from the earliest stages of infection. This balanced interplay between pro-inflammatory and regulatory signals may contribute to the clinical heterogeneity observed in Chagas disease and underscores the need to consider parasite diversity in pathogenic and therapeutic studies.

This study evaluated white turmeric (Curcuma zedoaria) as a sustainable feed additive alternative to common turmeric (C. longa) for enhancing disease resistance in Labeo rohita against Argulus siamensis infection. Juvenile L. rohita (15.8 ± 1.9 g) were divided into four treatment groups (n = 60 per group): (1) Control (commercial feed), (2) common turmeric-supplemented feed (1% w/w), (3) white turmeric-supplemented feed (1% w/w), and (4) combined turmeric-supplemented feed (0.5% common +0.5% white turmeric). Fish were fed experimental diets for 45 days before challenge with A. siamensis (10 parasites/fish), followed by 15 days of post-challenge monitoring (total experimental period: 60 days). Samples were collected on days 0, 15, 30, and 45 of the feeding phase, and on days 7 and 15 of the post-challenge phase. Results showed that turmeric supplementation significantly enhanced growth performance, haematological parameters (RBC, haemoglobin, haematocrit), immunological responses (lysozyme, respiratory burst, complement activities), and antioxidant status (SOD, CAT, MDA) compared to control. Post-challenge, turmeric-supplemented groups exhibited reduced parasite load and higher survival rates (Combined: 92%, common turmeric: 85%, White turmeric: 82%, Control: 68%). While common turmeric performed slightly better than white turmeric when used alone, the combined treatment showed superior efficacy in all parameters measured. These findings suggest that combining both turmeric species provides optimal benefits, while white turmeric can serve as a partial substitute for common turmeric in fish feed formulations when resource sustainability is a priority, thus helping to reduce competition with human food resources.

Visceral leishmaniasis is a potentially fatal zoonosis with an increasing incidence. Most infected felines present the disease in its subclinical form and demonstrate greater resistance to parasitemia than dogs. However, the role of cellular immunity in felines is still poorly understood. This study measured serum levels of interleukin (IL)-12 and interferon-gamma (IFN-γ) in asymptomatic cats naturally infected with antibodies against Leishmania spp. and in uninfected cats. IL-12 and IFN-γ were measured in serum samples by ELISA. Parasite load quantification was performed on DNA from bone marrow samples using qPCR. Cats naturally infected by Leishmania spp. showed significantly higher serum levels of IL-12 and IFN-γ compared to control animals. IL-12 showed a positive correlation with IFN-γ suggesting a regulatory role of IL-12 in activating the Th1 immune response, which enhances macrophage function and promotes intracellular parasite elimination. Additionally, IL-12 showed a moderate negative correlation with parasite load, indicating a protective effect of IL-12 in feline leishmaniasis. These findings suggest that IL-12 and IFN-γ play critical roles in modulating the feline immune response against parasitic infection, possibly contributing to the control of parasite replication and in the prevention of clinical signs. The immune response observed in felines could be explored for future immunotherapeutic approaches, helping to mitigate the progression of leishmaniasis in cats and reducing the risk of transmission in endemic regions.

Osteoarthritis (OA), a degenerative condition, severely impacts the quality of life in elderly individuals. Current clinical treatment options for OA remain limited. The polarisation of synovial macrophages plays a pivotal role in OA progression. SJMHE1, a peptide derived from Schistosoma japonicum (S. japonicum), has demonstrated the ability to inhibit inflammatory responses such as those seen in asthma and enteritis. Herein, SJMHE1 was administered via intra-articular injection to rats with anterior cruciate ligament transection (ACLT)-induced OA. Its effects on synovial inflammation, cartilage degradation and macrophage polarisation were assessed. Additionally, SJMHE1-stimulated macrophages were co-cultured with chondrocytes to examine chondrocyte degradation and apoptosis. The effect of the peptide on the expression of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) derived from patients with OA was also evaluated. SJMHE1 treatment delayed OA progression in elderly rats. It inhibited M1 macrophage polarisation, promoted M2 macrophage polarisation, reduced synovial inflammation and alleviated cartilage degradation. In the synovium, SJMHE1 downregulated proinflammatory cytokine IL-6 and upregulated the anti-inflammatory cytokine IL-10. In vitro, SJMHE1-treated macrophages preserved chondrogenic properties and inhibited chondrocyte apoptosis. Furthermore, SJMHE1 suppressed inflammatory cytokine production in PBMCs from patients with OA. The results suggest that SJMHE1 could represent a potential therapeutic approach for managing OA.

The severity of malaria is associated with low antioxidant availability and elevated free radical production, which induces oxidative damage in cerebral and pulmonary microcirculation. This can be mitigated by dietary antioxidants. We investigated the protective effects of lycopene (LYC) against oxidative changes induced by Plasmodium berghei (Pb). Mice were infected by intraperitoneal injection of 10⁶ parasitized red blood cells and treated orally with LYC (3.11 mg/kg bw/day) or N-acetylcysteine (NAC, 62 mg/kg bw/day). Evaluations were conducted at 1-, 4-, 8- and 12-days post-infection. We measured thiobarbituric acid reactive substances (TBARS), antioxidant capacity by ABTS (AC-ABTS) and DPPH (AC-DPPH) inhibition, uric acid (UA) and nitric oxide (NO) in brain and lung tissues. Infection led to elevated TBARS, AC-ABTS, AC-DPPH, UA and NO, resulting in animal mortality. LYC significantly attenuated the infection-induced increases in TBARS, UA and NO levels compared to Pb (p < 0.0001) and NAC + Pb groups (p < 0.0001) normalising them to Sham levels. These findings highlight LYC's therapeutic potential against malaria-related oxidative stress.

Kala-azar, or visceral leishmaniasis (VL), is a parasitic disease caused by Leishmania spp., characterised by fever, weight loss, splenomegaly, hepatomegaly, and anaemia. This study evaluated the relationship between hepcidin, inflammation, iron metabolism, and hypersplenism in VL-associated anaemia. In this cross-sectional study, confirmed VL patients without recent transfusions were assessed. Haematological and inflammatory parameters were analysed using correlation and multivariate regression tests. Anaemia was present in 95.2% of the sample, predominantly normocytic (59.5%) and normochromic (76.2%), or microcytic (40.5%) and hypochromic (23.8%). Inflammatory markers were markedly elevated in most patients, particularly hepcidin, which was increased in 97.6% of cases (median: 351.46 ng/mL), suggesting persistent inflammation and impaired iron bioavailability. However, IL-6, CRP, and ferritin showed weak to moderate negative correlations with hepcidin (ρ = -0.33, ρ = -0.66, and ρ = -0.30, respectively). These findings highlight the complex interplay between anaemia and inflammation in kala-azar, with elevated hepcidin levels and paradoxical correlations with inflammatory markers. They underscore the central role of splenomegaly in VL-related anaemia and suggest potential contributions from other factors affecting iron metabolism, such as erythropoietin and erythroferrone. Understanding the dynamics of these markers throughout disease progression and treatment may further elucidate the pathophysiology of VL and support the development of targeted therapies.