Explore the vast range of titles available.

Enterotoxaemia is a disease with a high associated mortality rate, affecting beef and veal calves worldwide, caused by C. perfringens alpha toxin and perfringolysin. A longitudinal study was conducted to determine the dynamics of antibodies against these toxins in 528 calves on 4 beef and 15 veal farms. The second study aimed to determine the effect of solid feed intake on the production of antibodies against alpha toxin and perfringolysin. The control group only received milk replacer, whereas in the test group solid feed was provided. Maternal antibodies for alpha toxin were present in 45% of the veal calves and 66% of the beef calves. In beef calves a fluent transition from maternal to active immunity was observed for alpha toxin, whereas almost no veal calves developed active immunity. Perfringolysin antibodies significantly declined both in veal and beef calves. In the second study all calves were seropositive for alpha toxin throughout the experiment and solid feed intake did not alter the dynamics of alpha and perfringolysin antibodies. In conclusion, the present study showed that veal calves on a traditional milk replacer diet had significantly lower alpha toxin antibodies compared to beef calves in the risk period for enterotoxaemia, whereas no differences were noticed for perfringolysin.

Sialic acids at the cell surface of dendritic cells (DCs) play an important immunomodulatory role, and their manipulation enhances DC maturation, leading to heightened T cell activation. Particularly, at the molecular level, the increased stability of surface MHC-I molecules in monocyte-derived DCs (MoDCs) underpins an improved DC: T cell interaction. In this study, we focused on the impact of sialic acid remodelling by treatment with Clostridium perfringens sialidase on MoDCs' phenotypic and functional characteristics. Our investigation juxtaposes this novel approach with the conventional cytokine-based maturation regimen commonly employed in clinical settings.Notably, C. perfringens sialidase remarkably increased MHC-I levels compared to other sialidases having different specificities, supporting the idea that higher MHC-I is due to the cleavage of specific sialoglycans on cell surface proteins. Sialidase treatment induced rapid elevated surface expression of MHC-I, MHC-II and CD40 within an hour, a response not fully replicated by 48 h cytokine cocktail treatment. These increases were also observable 48 h post sialidase treatment. While CD86 and PD-L1 showed significant increases after 48 h of cytokine maturation, 48 h post sialidase treatment showed a higher increase in CD86 and shorter increase in PD-L1. CCR-7 expression was significantly increased 48 h after sialidase treatment but not significantly affected by cytokine maturation. Both treatments promoted higher secretion of the IL-12 cytokine. However, the cytokine cocktail induced a more pronounced IL-12 production. SNA lectin staining analysis demonstrated that the sialic acid profile is significantly altered by sialidase treatment, but not by the cytokine cocktail, which causes only slight sialic acid upregulation. Notably, the lipid-presenting molecules CD1a, CD1b and CD1c remained unaffected by sialidase treatment in MoDCs, a finding also further supported by experiments performed on C1R cells. Inhibition of endogenous sialidases Neu1 and Neu3 during MoDC differentiation did not affect surface MHC-I expression and cytokine secretion. Yet, sialidase activity in MoDCs was minimal, suggesting that sialidase inhibition does not significantly alter MHC-I-related functions. Our study highlights the unique maturation profile induced by sialic acid manipulation in MoDCs. These findings provide insights into the potential of sialic acid manipulation as a rapid immunomodulatory strategy, offering promising avenues for targeted interventions in inflammatory contexts.

Clostridium perfringens is an anaerobic, toxin-producing pathogen responsible for enteric and systemic disease in livestock, yet its ecology in high-altitude yaks remains poorly understood. We conducted a comprehensive investigation covering eight counties of the Xizang Autonomous Region between July 2021 and October 2024. Serological screening of 922 unvaccinated yaks revealed an individual-level antibody prevalence of 0.76% (95% CI: 0.4–1.6) and a herd-level prevalence of 25% (95% CI: 12.7–43.4). Multivariable logistic regression identified residence below 4000 m as the sole significant risk factor (adjusted OR = 8.75; 95%CI: 1.3–56.8; P  = 0.04). From seven seropositive animals, one representative isolate CPTibet-Y1 was obtained and subjected to detailed phenotypic, genomic and virulence analyses. Phenotypic profiling confirmed classic biochemical traits of C. perfringens , while 16 S rRNA, Toxin gene PCR typing and whole-genome sequencing classified the strain as toxin type A, harboring Toxin gene cpa , but lacking cpb , etx , iap , cpe and netB . Antimicrobial resistance profiling revealed broad-spectrum resistance encompassing sulfonamides, lincosamides and fluoroquinolones, underpinned by six acquired resistance determinants. In a murine infection model, intraperitoneal challenge with 5 × 10 7 CFU resulted in 100% lethality within 48 h accompanied by severe intestinal necrosis, hemorrhage and systemic pathology. This study provides unequivocal evidence for the presence of multidrug-resistant, hypervirulent type A strains on the Qinghai-Tibet Plateau, underscoring the need for enhanced surveillance and targeted control strategies in yak-farming communities.

Clostridium perfringens α-toxins are lethal, neurotoxic factors that play a critical role in the pathogenesis of gas gangrene and hemorrhagic enteritis. In this study, the full-length α-toxin protein and two multi-epitope tandem proteins, CPA1 and CPA2, were recombinantly expressed using a prokaryotic expression system, and their immunogenic effects were evaluated in a mouse model. Compared with the full-length α-toxin, CPA1 and CPA2 induced comparable lymphocyte proliferation and differentiation, as well as sustained high antibody levels. Additionally, significantly elevated serum levels of cytokines IL-2, IL-4, and IL-10 were observed in mice immunized with CPA1 and CPA2. Protective efficacy against lethal toxin challenge was 70 % for CPA1 and 80 % for CPA2, as assessed relative to the α-toxin protein control. These findings suggest that CPA1 and CPA2 represent promising subunit vaccine candidates against Clostridium perfringens type A infection in sika deer.

We have isolated Clostridium perfringens type B, an epsilon toxin-secreting bacillus, from a young woman at clinical presentation of Multiple Sclerosis (MS) with actively enhancing lesions on brain MRI. This finding represents the first time that C. perfringens type B has been detected in a human. Epsilon toxin's tropism for the blood-brain barrier (BBB) and binding to oligodendrocytes/myelin makes it a provocative candidate for nascent lesion formation in MS. We examined a well-characterized population of MS patients and healthy controls for carriage of C. perfringens toxinotypes in the gastrointestinal tract. The human commensal Clostridium perfringens type A was present in approximately 50% of healthy human controls compared to only 23% in MS patients. We examined sera and CSF obtained from two tissue banks and found that immunoreactivity to ETX is 10 times more prevalent in people with MS than in healthy controls, indicating prior exposure to ETX in the MS population. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation since these lesions are characterized by BBB permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate.

Necrotic enteritis is an economically important poultry disease caused by the bacterium Clostridium perfringens. There are currently no necrotic enteritis vaccines commercially available for use in broiler birds, the most important target population. Salmonella-vectored vaccines represent a convenient and effective option for controlling this disease. We used a single attenuated Salmonella vaccine strain, engineered to lyse within the host, to deliver up to three C. perfringens antigens. Two of the antigens were toxoids, based on C. perfringens α-toxin and NetB toxin. The third antigen was fructose-1,6-bisphosphate aldolase (Fba), a metabolic enzyme with an unknown role in virulence. Oral immunization with a single Salmonella vaccine strain producing either Fba, α-toxoid and NetB toxoid, or all three antigens, was immunogenic, inducing serum, cellular and mucosal responses against Salmonella and the vectored C. perfringens antigens. All three vaccine strains were partially protective against virulent C. perfringens challenge. The strains delivering Fba only or all three antigens provided the best protection. We also demonstrate that both toxins and Fba are present on the C. perfringens cell surface. The presence of Fba on the cell surface suggests that Fba may function as an adhesin.

( ), a ubiquitous Gram-positive bacterium in the environment and mammalian gut flora, is a leading cause of enterotoxemia in animals, necrotizing enteritis in humans and animals, and gas gangrene in both, attributed to its diverse exotoxin profile. Alpha-toxin, a pivotal virulence factor produced by all serotypes, plays a central role in the pathogenicity of these diseases. Here, we engineered a lipid nanoparticle encapsulated CPA-CTD mRNA vaccine targeting the conserved C-terminal domain of alpha-toxin and rigorously assessed its immunogenicity and protective efficacy in mouse and bovine models. The CPA-CTD mRNA vaccine induced strong humoral and cellular immune responses in mice, particularly in promoting the rapid production of specific IgG and mucosal IgA antibodies, as well as enhancing T cell immune responses, surpassing conventional subunit vaccines. Protection was confirmed in dual challenge models --enterotoxemia and gas gangrene --where the vaccine provided complete immunity against lethal doses of alpha-toxin and infection. In cattle, the CPA-CTD mRNA vaccine induced high-titer IgG antibodies and toxin-neutralizing antibodies. Notably, immunization of pregnant cows led to efficient transfer of these antibodies via colostrum to newborn calves, providing passive protection. These results demonstrate that the CPA-CTD mRNA vaccine provides rapid and robust immune protection against alpha-toxin-associated diseases, with promising potential for applications in both veterinary and human health.

The Clostridium-related poultry disease, necrotic enteritis (NE), causes substantial economic losses on a global scale. In the present study, a mixture of two plant-derived phytonutrients, Capsicum oleoresin and turmeric oleoresin (XT), was evaluated for its effects on local and systemic immune responses using a co-infection model of experimental NE in commercial broilers. Chickens were fed from hatch with a diet supplemented with XT, or with a non-supplemented control diet, and either uninfected or orally challenged with virulent Eimeria maxima oocysts at 14 d and Clostridium perfringens at 18 d of age. Parameters of protective immunity were as follows: (1) body weight; (2) gut lesions; (3) serum levels of C. perfringens α-toxin and NE B-like (NetB) toxin; (4) serum levels of antibodies to α-toxin and NetB toxin; (5) levels of gene transcripts encoding pro-inflammatory cytokines and chemokines in the intestine and spleen. Infected chickens fed the XT-supplemented diet had increased body weight and reduced gut lesion scores compared with infected birds given the non-supplemented diet. The XT-fed group also displayed decreased serum α-toxin levels and reduced intestinal IL-8, lipopolysaccharide-induced TNF-α factor (LITAF), IL-17A and IL-17F mRNA levels, while cytokine/chemokine levels in splenocytes increased in the XT-fed group, compared with the animals fed the control diet. In conclusion, the present study documents the molecular and cellular immune changes following dietary supplementation with extracts of Capsicum and turmeric that may be relevant to protective immunity against avian NE.

Absent in melanoma 2 (AIM2), a key component of the IFI20X/IFI16 (PYHIN) protein family, is characterized as a DNA sensor to detect cytosolic bacteria and DNA viruses. However, little is known about its immunological role during pathogenic Clostridium perfringens (C. perfringens) infection, an extracellular bacterial pathogen. In a pathogenic C. perfringens gas gangrene model, Aim2−/− mice are more susceptible to pathogenic C. perfringens soft tissue infection, revealing the importance of AIM2 in host protection. Notably, Aim2 deficiency leads to a defect in bacterial killing and clearance. Our in vivo and in vitro findings further establish that inflammasome signaling is impaired in the absence of Aim2 in response to pathogenic C. perfringens. Mechanistically, inflammasome signaling downstream of active AIM2 promotes pathogen control. Importantly, pathogenic C. perfringens-derived genomic DNA triggers inflammasome signaling activation in an AIM2-dependent manner. Thus, these observations uncover a central role for AIM2 in host defense and triggering innate immunity to combat pathogenic C. perfringens infections.

is the primary causative agent of enterotoxemia in yaks, resulting in substantial economic losses on the Qinghai-Tibet Plateau. Conventional vaccines exhibit limited protective breadth and suboptimal efficacy, highlighting the need for innovative strategies. Here, we aimed to construct a novel vaccine candidate incorporating epitopes from multiple prevalent toxinotypes (A, C, E) of affecting yaks, using immunoinformatics approach. A hierarchical immunoinformatics pipeline was implemented, encompassing subtractive genomics to identify core virulence factors, prediction and filtering of immunogenic T-cell and B-cell epitopes, rational multi-epitope vaccine design incorporating adjuvant and linkers, three-dimensional structure modeling and validation, molecular docking to evaluate interactions with TLR4, molecular dynamics simulations to confirm complex stability, and codon optimization to facilitate heterologous expression. Five core virulence proteins ( , , , , ) were identified from genomic data, leading to the prediction and selection of ten cytotoxic T lymphocyte (CTL) epitopes, five helper T lymphocyte (HTL) epitopes, and five B-cell epitopes. The final 352-amino-acid multi-epitope vaccine (MEV) construct was assembled using the adjuvant human β-defensin-3 and specific linkers (AAY, GPGPG, KK). Computational evaluations confirmed the vaccine's high antigenicity (VaxiJen score: 0.9092), non-allergenic nature, and structural stability. Molecular docking revealed strong binding affinity with TLR2 (-1024.6 kcal/mol) and TLR4 (-1104.4 kcal/mol). Molecular dynamics simulations over 100 ns confirmed stable TLR4 complex with an average RMSD of 0.1971 ± 0.0377 nm, while the TLR2 complex showed an average RMSD of 0.2692 ± 0.0420 nm. Immune simulation profiles predicted the induction of robust humoral and cellular immune responses, including elevated antibody titers, T-cell activation, and cytokine production. cloning verified the potential for efficient expression in E. coli. This study designed a novel multi-epitope vaccine against in yaks using an immunoinformatics approach. The vaccine showed high antigenicity, stability, and broad allelic coverage , providing a promising candidate that requires rigorous and experimental validation to confirm these computational predictions. This work offers a foundation for the development of effective vaccines against yak infections on the Qinghai-Tibet Plateau.