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Background and Aim: Cattle are the main source of meat in Benin. To improve the attitudes and practices of cattle breeders in relation to bovine brucellosis, a study has been carried out in Benin according to different agroecological zones. This study aimed to assess farmers' knowledge and practices concerning bovine brucellosis to generate essential information for control programs and public health interventions. Materials and Methods: The study was conducted from February to May 2022, during which 608 farmers were interviewed using a structured questionnaire that provided information on socioeconomic characteristics, knowledge, and practices related to bovine brucellosis. Analysis of variance, Poisson regression, and the proportion comparison test were used to compare these characteristics in the different agroecological zones. At the end of the surveys, three distinct and homogeneous groups of perceptions (hierarchical classification of Multiple Correspondence Analysis components of R software) of bovine brucellosis were identified (these groups only consider farmers who declared knowledge of the disease). Groups were formed by applying the multiple correspondence analysis function of the FactoMineR library in R software, followed by a hierarchical ascending classification using the hierarchical clustering on principal component function of the same software (Agrocampus Rennes, France). Results: Only 38% of respondents were aware of brucellosis. Knowledge of brucellosis was not related to sex or education level but was higher among farmers in agroecological Zones 1 and 4. Ethnic Dendi herders (62.16%) had better knowledge of the disease than those from other sociolinguistic groups (Somba: 50%, Fulani: 40.91%, Baribas: 26.97%, and others: 8.82%). Reduced milk production (98.29%), presence of hygroma (87.18%), and abortion (56.84%) are the main signs reported by herders familiar with the disease. All three groups had good knowledge of the disease and its zoonotic nature. Groups 1 (96% of breeders) and 2 (2.14%) were aware of the risk factors (contact with affected animals, the consumption of raw milk, the handling of runts, and reproductive rejection). In the case of Brucella, they prefer to treat animals rather than sell them and use both traditional and modern medicines. Group 3 (1.71%) did not know the risk factors and preferred to sell animals in the event of illness. Conclusion: Pastoralists need to be made aware of the mode of transmission of bovine brucellosis, its clinical manifestations, its impact on animal health, and the zoonotic nature of the disease (impact on public health) so that bovine brucellosis can be rapidly detected in herds. [ABSTRACT FROM AUTHOR]

Mtb (Mycobacterium tuberculosis) is a pathogenic bacterium that causes tuberculosis infection (TB). Mtb -secreted proteins have recently been investigated as virulence factors, as well as therapeutic and vaccine possibilities. The early-secreted antigen target MTB48 is one of these proteins that has been explored as a cocktail antigen in the serodiagnosis of active tuberculosis. However, there exists no information about the function or control of MTB48's inflammatory activity in macrophages at the site of inflammation. As a result, the goal of this research was to figure out what processes are involved in MTB48's function. MTB48 stimulated inflammation in LPS induced macrophages at both the protein and mRNA levels, which was interesting. MTB48 aided LPS induced IB phosphorylation and NF-κB translocation. MTB48 also led to the phosphorylation of MAPK signaling protein. These findings imply that MTB48 can enhance inflammatory activity via NF-κB and MAPK signaling by upregulating COX-2, iNOS, NO and PGE 2. Many tuberculosis antigens have been tested for the development of rapid serological diagnosis. The results of this study suggest that MTB48 is a very high conservative antigen and is a major factor causing inflammatory reactions, suggesting that it can help control and diagnose tuberculosis. [Display omitted] • The function and control of the Mtb-secreted protein MTB48's inflammatory activity in macrophages at the site of inflammation. • MTB48 enhanced inflammatory activity via NF-κB and MAPK signaling by upregulating COX-2, iNOS, NO, and PGE2. • MTB48 could be a potential target for therapeutic and vaccine possibilities, as well as a diagnostic tool for active tuberculosis. • MTB48 is a highly conservative antigen and a major factor in causing inflammatory reactions. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis and paratuberculosis are endemic in many areas worldwide. This work aims to study cytokines production and gene expression profiles of bovine macrophages infected with Mycobacterium bovis and Mycobacterium paratuberculosis subsp. avium (MAP) strains to identify potential diagnostic biomarkers. Bovine bone marrow stem cells were differentiated into macrophages and subsequently infected in vitro with different spoligotypes of M. bovis and MAP field strains (as single infections and coinfections), using different multiplicity of infection. Supernatant and cell pellets were collected 24 h, 48 h, and one week post-infection. Preliminarily, gene expression on cell pellets of IL-1β, IL-2, INFγ, IL-6, IL-10, IL-12, and TNFα was assessed by qRT-PCR one week p.i. Subsequently, IL-1β and IL-6 were measured by ELISA and qRT-PCR to investigated their production retrospectively 24 h and 48 h p.i. A variability in macrophages response related to the concentration of mycobacteria, the coinfection with MAP, and M. bovis spoligotypes was identified. An early and constant IL-6 increase was observed in the M. bovis infection. A lower increase in IL-1β was also detected at the highest concentration of the two M. bovis spoligotypes one week post-infection. IL-6 and IL-1 β production was reduced and differently expressed in the MAP infection. IL-6 appeared to be the earliest cytokines produced by bovine macrophages infected with M. bovis. [ABSTRACT FROM AUTHOR]

Total ring depopulation is sometimes used as a management strategy for emerging infectious diseases in livestock, which raises ethical concerns regarding the potential slaughter of large numbers of healthy animals. We evaluated a farm-density-based ring culling strategy to control foot-and-mouth disease (FMD) in the United Kingdom (UK), which may allow for some farms within rings around infected premises (IPs) to escape depopulation. We simulated this reduced farm density, or "target density", strategy using a spatially-explicit, stochastic, state-transition algorithm. We modeled FMD spread in four counties in the UK that have different farm demographics, using 740,000 simulations in a full-factorial analysis of epidemic impact measures (i.e., culled animals, culled farms, and epidemic length) and cull strategy parameters (i.e., target farm density, daily farm cull capacity, and cull radius). All of the cull strategy parameters listed above were drivers of epidemic impact. Our simulated target density strategy was usually more effective at combatting FMD compared with traditional total ring depopulation when considering mean culled animals and culled farms and was especially effective when daily farm cull capacity was low. The differences in epidemic impact measures among the counties are likely driven by farm demography, especially differences in cattle and farm density. To prevent over-culling and the associated economic, organizational, ethical, and psychological impacts, the target density strategy may be worth considering in decision-making processes for future control of FMD and other diseases. [ABSTRACT FROM AUTHOR]

There is still incomplete knowledge of which Mycobacterium tuberculosis (Mtb) antigens can trigger distinct T cell responses at different stages of infection. Here, a proteome-wide screen of 20,610 Mtb-derived peptides in 21 patients mid-treatment for active tuberculosis (ATB) reveals IFNγ-specific T cell responses against 137 unique epitopes. Of these, 16% are recognized by two or more participants and predominantly derived from cell wall and cell processes antigens. There is differential recognition of antigens, including TB vaccine candidate antigens, between ATB participants and interferon-gamma release assay (IGRA + /−) individuals. We developed an ATB-specific peptide pool (ATB116) consisting of epitopes exclusively recognized by ATB participants. This pool can distinguish patients with pulmonary ATB from IGRA + /− individuals from various geographical locations, with a sensitivity of over 60% and a specificity exceeding 80%. This proteome-wide screen of T cell reactivity identified infection stage-specific epitopes and antigens for potential use in diagnostics and measuring Mtb-specific immune responses. T cells play critical roles in the immune pathology of tuberculosis. Here the authors perform a proteome-wide screen of T cell antigens and reactivity to mycobacterium tuberculosis at different stages of infection. [ABSTRACT FROM AUTHOR]

Robertsonian translocation 1;29 (rob(1;29)), a widespread chromosomal anomaly affecting cattle fertility, appears to have originated from a common ancestor. This study utilizes routine SNP data to investigate the chromosomal region associated with rob(1;29) and confirm the presence of a shared haplotype among carriers in diverse Italian breeds. Three datasets were employed: Dataset 1 included 151 subjects from 5 beef cattle breeds genotyped with the GGP Bovine 33 k SNP chip; Dataset 2 encompassed 800 subjects from 32 Italian breeds genotyped with the Illumina 50 k SNP chip, sourced from the BOVITA dataset; Dataset 3 combined Dataset 2 with 21 karyologically tested subjects from breeds with a high carrier frequency, genotyped using the Affymetrix 65 K SNP chip. FST analysis pinpointed a distinctive genomic region on the first six Mb of BTA29, the centromeric region involved in the translocation. Haplotype comparisons within this non-recombining region revealed a common haplotype shared among all carriers, supporting the theory of a common ancestor. Principal component and haplotype analysis allowed clear differentiation of rob(1;29) homozygous and heterozygous carriers. Expanding to Dataset 2 revealed rob(1;29) carriers in unexpected breeds, all sharing the same ancestral haplotype. Notably, previously untested breeds, including Cinisara, exhibited a high carrier prevalence (nearly 50%), confirmed by karyological analysis. This study validates the presence of a shared haplotype among all identified rob(1;29) carriers, reinforcing the common ancestor theory as the origin of this translocation's spread throughout the cattle population. Furthermore, it underscores the potential of SNP data analysis as a rapid, accurate, and cost-effective tool for broad rob(1;29) screening, given the translocation's consistent nature across all analyzed breeds. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (bTB) is a zoonotic disease that is commonly transmitted via inhaling aerosols, drinking unpasteurized milk, and eating raw meat. We use a fractional-order model with the Caputo sense to examine the evolution of bovine tuberculosis transmission in human and animal populations, including a vaccine compartment for humans. We derived and obtained the threshold quantity R 0 to ascertain the illness state. We established conditions guaranteeing the asymptotic stability of the equilibria (locally and globally). Sensitivity analysis was conducted to identify the factors that govern the dynamics of tuberculosis. The study demonstrates that the rate of human-to-animal transmission of tuberculosis and environmental pollution and the rate of bTB transmission between animals all affect tuberculosis transmission. However, as vaccination rates increase and fewer individuals consume contaminated environment products (such as meat, milk, and other dairy products), the disease becomes less common in humans. To manage bovine TB, it is advised that information programmes be implemented, the environment be monitored, infected persons be treated, contaminated animals be vaccinated, and contaminated animals be quarantined. The usefulness of the discovered theoretical results is demonstrated through numerical experiments. [ABSTRACT FROM AUTHOR]

Alveolar macrophages (AMs) play a critical role during Mycobacterium tuberculosis (Mtb) infection as the first cells in the lung to encounter bacteria. We previously showed that AMs initially respond to Mtb in vivo by mounting a cell-protective, rather than pro-inflammatory response. However, the plasticity of the initial AM response was unknown. Here, we characterize how previous exposure to Mycobacterium, either through subcutaneous vaccination with Mycobacterium bovis (scBCG) or through a contained Mtb infection (coMtb) that mimics aspects of concomitant immunity, impacts the initial response by AMs. We find that both scBCG and coMtb accelerate early innate cell activation and recruitment and generate a stronger pro-inflammatory response to Mtb in vivo by AMs. Within the lung environment, AMs from scBCG vaccinated mice mount a robust interferon-associated response, while AMs from coMtb mice produce a broader inflammatory response that is not dominated by Interferon Stimulated Genes. Using scRNAseq, we identify changes to the frequency and phenotype of airway-resident macrophages following Mycobacterium exposure, with enrichment for both interferon-associated and pro-inflammatory populations of AMs. In contrast, minimal changes were found for airway-resident T cells and dendritic cells after exposures. Ex vivo stimulation of AMs with Pam3Cys, LPS and Mtb reveal that scBCG and coMtb exposures generate stronger interferon-associated responses to LPS and Mtb that are cell-intrinsic changes. However, AM profiles that were unique to each exposure modality following Mtb infection in vivo are dependent on the lung environment and do not emerge following ex vivo stimulation. Overall, our studies reveal significant and durable remodeling of AMs following exposure to Mycobacterium, with evidence for both AM-intrinsic changes and contributions from the altered lung microenvironments. Comparisons between the scBCG and coMtb models highlight the plasticity of AMs in the airway and opportunities to target their function through vaccination or host-directed therapies. Author summary: Tuberculosis, a disease caused by the bacteria Mycobacterium tuberculosis (Mtb), claims around 1.6 million lives each year, making it one of the leading causes of death worldwide by an infectious agent. Based on principles of conventional immunological memory, prior exposure to either Mtb or M. bovis BCG leads to antigen-specific long-lasting changes to the adaptive immune response that can be effective at protecting against subsequent challenge. However, how these exposures may also impact the innate immune response is less understood. Alveolar macrophages are tissue-resident myeloid cells that play an important role during Mtb infection as innate immune sentinels in the lung and the first host cells to respond to infection. Here, we examined how prior Mycobacterium exposure, either through BCG vaccination or a model of contained Mtb infection, impacts the early innate response by alveolar macrophages. We find that prior exposure remodels the alveolar macrophage response to Mtb through both cell-intrinsic changes and signals that depend on the altered lung environment. These findings suggest that the early innate immune response could be targeted through vaccination or host-directed therapy and could complement existing strategies to enhance the host response to Mtb. [ABSTRACT FROM AUTHOR]

Introduction: The family Mycobacteriaceae contains over 188 species, most of which are saprophytic non-tuberculous mycobacteria (NTM). In wildlife, a variety of different NTM can be found, with different reports about their pathogenic potential. A pathogenic member of NTM is Mycobacterium avium ssp. paratuberculosis (MAP), which can infect farmed and wild ruminants. It causes paratuberculosis which is an economically important chronic disease. Infected farm animals are considered to be the source of infection in wild animals. Wildlife, on the other hand, is thought to be a reservoir for certain members of the Mycobacterium tuberculosis complex (MTBC), such as M. caprae, which causes tuberculosis in cattle and red deer. Methods: Switzerland implemented a surveillance program for tuberculosis in wild animals in 2014. Here, we describe the results from the mycobacterial culture of lymph node samples collected from red deer, roe deer, chamois, ibex, and badgers collected within this surveillance program from 2020 to 2022. Overall, samples from 548 animals were checked macroscopically for tuberculosis-like lesions. Results: In total, 88 animals (16.1%), which either had lesions in their lymph nodes or were male and aged older than 5 years, were investigated using mycobacterial culture. In total, 25 animals (28.4%) were positive for NTM, while no MTBC was detected. The most often identified NTM was M. vaccae, followed by M. avium. Most animals positive for NTM did not show any macroscopic lesions. Furthermore, MAP was isolated from the head lymph nodes of two male red deer. Neither of the two MAP-positive animals had any macroscopic lesions in their head lymph nodes or any other signs of disease. Discussion: The shooting sites of the two MAP-positive animals were located in Alpine pastures used for grazing of cattle during summer, which confirms that species transmission can occur when contaminated pastures are used by different species. In agreement with other studies, the occurrence of MAP in red deer was quite low. However, so far, MAP was mostly isolated from feces and intestinal lymph nodes of wild animals. This is the first detection of MAP in the head lymph nodes of red deer in Switzerland. [ABSTRACT FROM AUTHOR]

Simple Summary: The in vitro production (IVP) of bovine embryos has increased in popularity in the past few decades with improvements in our ability to harvest oocytes from genetically elite heifers and cows, fertilize them in vitro, and successfully culture embryos to the stage where they can be transferred. One issue with IVP is that the efficiency of embryo production is less than ideal. One likely reason for the poor development of IVP embryos is the excessive exposure of oocytes and embryos to reactive oxygen species (ROS). These molecules are produced as a normal by-product of energy generation; however, excess accumulation of ROS during the IVP of oocyte and embryo culture will damage nucleic acids, lipids, and proteins in ways that compromise development potential and post-transfer embryo survival. Molecules that react with and block ROS-induced damage are commonly referred to as antioxidants. This review explores the use of five common antioxidants to limit ROS-induced damage and promote the IVP of embryos. The in vitro production (IVP) of bovine embryos has gained popularity worldwide and in recent years and its use for producing embryos from genetically elite heifers and cows has surpassed the use of conventional superovulation-based embryo production schemes. There are, however, several issues with the IVP of embryos that remain unresolved. One limitation of special concern is the low efficiency of the IVP of embryos. Exposure to reactive oxygen species (ROS) is one reason why the production of embryos with IVP is diminished. These highly reactive molecules are generated in small amounts through normal cellular metabolism, but their abundances increase in embryo culture because of oocyte and embryo exposure to temperature fluctuations, light exposure, pH changes, atmospheric oxygen tension, suboptimal culture media formulations, and cryopreservation. When uncontrolled, ROS produce detrimental effects on the structure and function of genomic and mitochondrial DNA, alter DNA methylation, increase lipid membrane damage, and modify protein activity. Several intrinsic enzymatic pathways control ROS abundance and damage, and antioxidants react with and reduce the reactive potential of ROS. This review will focus on exploring the efficiency of supplementing several of these antioxidant molecules on oocyte maturation, sperm viability, fertilization, and embryo culture. [ABSTRACT FROM AUTHOR]

The European badger, Meles meles, is an important wildlife host for Mycobacterium bovis and contributes to the epidemiology of bovine tuberculosis (bTB) in cattle in several countries. The control of zoonotic diseases, such as bTB, is a central component of global One-Health strategies. Such strategies are complicated by human–wildlife conflicts, particularly where wildlife reservoirs are legally protected. The contrasting objectives of disease management and wildlife conservation, therefore, can require significant investment in research to support evidence-based policies. In Britain and Ireland, for example, badgers are a legally protected species but are also subject to lethal control and vaccination for disease management. In this paper, we review recent (2012–2022) advances in research on this wildlife host on the island of Ireland, which is used to underpin national policies and identify research gaps. In recent years, significant advances in estimating key parameters related to badger management and population dynamics have been made, including estimating population abundance at varying scales (local, landscape, and national). Advances in tracking technology, integrated with mark-recapture and modelling tools, have provided significant insights into the movement ecology of badgers and their interactions with cattle. The adaptation of genetic technologies has improved our understanding of the transmission dynamics of M. bovis among different hosts. As a disease management strategy, the culling of badgers to control bTB has reduced badger densities significantly, although this is not considered a sustainable sole long-term solution to the problem of spillback infection. The recent development of vaccination strategies presents an additional approach to control the disease in wild populations. These types of interventions will require significant applied research to ensure they are sustainable and to maximise benefits. It is also expected that focused research efforts will improve human–wildlife coexistence in the context of the broader One-Health strategy. [ABSTRACT FROM AUTHOR]

Many pathogens of humans and livestock also infect wildlife that can act as a reservoir and challenge disease control or elimination. Efficient and effective prioritization of research and management actions requires an understanding of the potential for new tools to improve elimination probability with feasible deployment strategies that can be implemented at scale. Wildlife vaccination is gaining interest as a tool for managing several wildlife diseases. To evaluate the effect of vaccinating white-tailed deer (Odocoileus virginianus), in combination with harvest, in reducing and eliminating bovine tuberculosis from deer populations in Michigan, we developed a mechanistic age-structured disease transmission model for bovine tuberculosis with integrated disease management. We evaluated the impact of pulse vaccination across a range of vaccine properties. Pulse vaccination was effective for reducing disease prevalence rapidly with even low (30%) to moderate (60%) vaccine coverage of the susceptible and exposed deer population and was further improved when combined with increased harvest. The impact of increased harvest depended on the relative strength of transmission modes, i.e., direct vs indirect transmission. Vaccine coverage and efficacy were the most important vaccine properties for reducing and eliminating disease from the local population. By fitting the model to the core endemic area of bovine tuberculosis in Michigan, USA, we identified feasible integrated management strategies involving vaccination and increased harvest that reduced disease prevalence in free-ranging deer. Few scenarios led to disease elimination due to the chronic nature of bovine tuberculosis. A long-term commitment to regular vaccination campaigns, and further research on increasing vaccines efficacy and uptake rate in free-ranging deer are important for disease management. Author summary: Many wildlife species act as reservoirs of bovine tuberculosis from which they can transmit to cattle and humans. In Michigan, bovine tuberculosis is endemic in white-tailed deer causing occasional spillovers to cattle. Here, with the help of a disease transmission model, we explored the use of wildlife vaccination in white-tailed deer to manage bovine tuberculosis in Michigan. We show that pulse vaccination effectively reduces disease prevalence, especially when combined with increased deer harvest. Key vaccine parameters for disease elimination are vaccine coverage and efficacy. While complete elimination is challenging, sustained vaccination and research to improve vaccine effectiveness are crucial for long-term disease management. Hence, this research informs integrated strategies to reduce bovine tuberculosis in deer populations. [ABSTRACT FROM AUTHOR]

This paper gives an account of the history of veterinary bacteriology including clinical veterinary bacteriology as well as the area of veterinary public health in Denmark from the 1880s to 2022. We describe key persons, including B. Bang, C.O. Jensen, K.A. Jensen and others who made important contributions to the development of these areas of microbiological expertise, and we discuss how challenges ranging from bovine tuberculosis to bacterial antimicrobial resistance have been met. Further, we describe progress in research on important bacterial pathogens both with regard to animal clinical aspects and zoonotic food‐related aspects. Finally, we describe current issues in relation to One Health and research organization. [ABSTRACT FROM AUTHOR]

Background and Aim: Tuberculosis (TB) is a major zoonosis in Senegal, accounting for 33% of all zoonotic disease reports in 2019. The aim of this study was to assess bovine TB knowledge and practices of abattoir workers in Dakar and livestock farmers in Pout. Materials and Methods: We conducted a cross-sectional study on knowledge and practices of Dakar abattoir workers (butchers, transporters, sellers, and animal health workers) and Pout livestock farmers regarding bovine tuberculosis. R 3.2.6 was used for descriptive statistics, Chi-square, and Fischer's exact tests, and STATA 13 was used for univariate and multivariate logistic regressions. Results: A total of 274 abattoir workers and livestock farmers were interviewed: 103 (37.6%) from Dakar abattoir and 171 (62.4%) from Pout farms. Respondents were predominantly male (75.2%), aged 30-59 years (67.5%), and had at least 10 years of experience (51.8%). The majority (98.2%) were aware of TB, but only 31.4% knew that it was zoonotic. Only 2.5% (7/274) of participants had satisfactory TB knowledge, which differed according to study area, experience, profession, and good practice (p = 0.05). Abattoir workers were 11 times more likely than farmers to have good TB knowledge (odds ratio [OR] = 11.2; 95% confidence interval [CI] = 1.1-114.3). Respondents with 5-10 years of experience were 16.9 times more likely to have good knowledge of TB (OR = 16.9; 95% CI = 1.7-163.4). The majority of participants preferred raw milk (83.6%) and undercooked meat (83.6%). Only 29.6% of participants had good practices, which differed with respect to study area, gender, marital status, age, occupation, and knowledge of TB (p = 0.05). Age (OR = 3.3; 95% CI, 1.3-8.3) was identified as a good practice adoption predictor. Conclusion: Globally, there was a low level of good knowledge and practices regarding TB among respondents. There is a need for mass education through multi-sectoral collaboration between health professionals (humans and animals) using a One Health approach. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis, the etiological agent of tuberculosis, is one of the trickiest pathogens. We have only a few protective shields, like the BCG vaccine against the pathogen, which itself has poor efficacy in preventing adult tuberculosis. Even though different vaccine trials for an alternative vaccine have been conducted, those studies have not shown much promising results. In the current study, advanced computational technology was used to study the potential of a novel hypothetical mycobacterial protein, identified by subtractive hybridization, to be a vaccine candidate. NHP2 (Novel Hypothetical Protein 2), housed in the RD7 region of the clinical strains of M. tuberculosis, was studied for its physical, chemical, immunological and structural properties using different computational tools. PFAM studies and Gene ontology studies depicted NHP2 protein to be functionally active with a possible antibiotic binding domain too. Different computational tools used to assess the toxicity, allergenicity and antigenicity of the protein indicated its antigenic nature. Immune Epitope Database (IEDB) tools were used to study the T and B cell determinants of the protein. The 3D structure of the protein was designed, refined and authenticated using bioinformatics tools. The validated tertiary structure of the protein was docked against the TLR3 immune receptor to study the binding affinity and docking scores. Molecular dynamic simulation of the protein-protein complex formed were studied. NHP2 was found to activate host immune response against tubercle bacillus and could be explored as a potential vaccine in the fight against tuberculosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Bovine tuberculosis (bTB) is a contagious and notifiable disease, which is prevalent in cattle populations of many countries and in several wildlife species worldwide. However, the role of wildlife in the transmission and/or maintenance of bTB at the human-wild animal-animal interface and the epidemiology of zoonotic disease are poorly understood in Cameroon, where many wildlife species exist. This study aimed to estimate the prevalence and zoonotic risk factors of bTB at the cattle-wildlife-human interface in the South and East regions of Cameroon. Materials and Methods: We conducted a descriptive cross-sectional study from May to October 2022 in the southern region (Vallée du Ntem and Dja et Lobo) and eastern region (Haut Nyong and Lom et Djérem) of Cameroon to determine risk factors for bTB in Zebu Bororo, Goudali, Ndama, and Simmental cattle breeds. A comparative intradermal tuberculin testing (CIDT) was performed on 160 cattle randomly selected from herds using the threshold recommended by the World Organization for Animal Health. An interviewee-administered questionnaire was used to gather epidemiological data on sociodemographics, interaction between cattle and wildlife, and awareness of zoonotic tuberculosis (TB) from 90 cattle professionals. The prevalence of bTB at the herd level and associated risk factors were estimated using multiple logistic regression models. Results: Based on the comparative intradermal tuberculin test (CIDT), the estimated prevalence of bTB in 160 cattle (Zebu Bororo, Goudali, Ndama, and Simmental) in South and East Cameroon was 6.8% (4.35%-9.41%) and 1.8% (0%-3.6%) for threshold values 3 mm and 4 mm, respectively. The prevalence obtained by simple intradermal tuberculin test (IDT) was 0.6% (0%-1.2%) for a threshold value 4 mm. Univariate analysis revealed three risk factors associated with bTB with significant odds ratios (OR; p = 0.05): herd size (OR = 4.88; 95% confidence interval [CI]: 1.24-32.56); cattle aged>10 years (OR = 0.17; 95% CI: 0.05-0.53); and victims of bTB organ seizure (OR = 0.015; 95% CI: 0.002-0.067). Multivariate analysis showed that being a cattle herder and contact between wildlife and livestock due to forage was significantly associated with bTB exposure (adjusted OR = 0.02; p = 0.001). Conclusion: Bovine TB is prevalent in cattle of the South and East Cameroon. Comparative IDT of cattle reared in the epidemiological and environmental context of the study areas yielded better results at a threshold of 3 mm than at a threshold of 4 mm recommended by the World Health Organization. Factors associated with exposure to/appearance of bTB were high herd size, cattle aged >10 years old, seizures of tuberculous organs, shepherding as a profession, and contact between cattle and wildlife can be due to lack of forage. [ABSTRACT FROM AUTHOR]

Tritrichomonas foetus is a flagellated parasite that primarily infects the reproductive tissues of livestock, causing bovine trichomoniasis. The cytoplasmic membrane of T. foetus contains various compounds that contribute to adherence, colonization, and pathogenicity. Metronidazole (MTZ) is the main treatment for trichomoniasis, but the emergence of drug‐resistant strains is a concern due to improper use and dosing. T. foetus infection induces inflammation, and macrophages are key players in the immune response. However, our understanding of the host's immune response to T. foetus is limited, and the specific mechanisms underlying these responses are not well understood. This study aimed to investigate the impact of T. foetus surface proteins from trophozoites cultured under different sublethal MTZ conditions (MTZ‐treated T. foetus MPs) on macrophage activation. By analyzing cytokine levels and gene expression in murine macrophages, we demonstrated that MTZ‐treated T. foetus MPs induce a specific proinflammatory response. MTZ‐treated T. foetus MPs‐exposed macrophages exhibited a higher NO and H2O2 production and overexpression of iNOS and NOX‐2 genes in comparison to untreated T. foetus. Additionally, MTZ‐treated T. foetus MPs triggered a significant induction of the proinflammatory cytokines IL‐1β, IL‐6, TNF‐α, and IFN‐γ, as well as the overexpression of the TLR4, MyD88, and NF‐κB genes on murine macrophages. The study aimed to unravel the immunological response and potential proinflammatory pathways involved in T. foetus infection and MTZ stress. Understanding the immune responses and mechanisms through which T. foetus surface proteins activate macrophages can contribute to the development of new therapeutic strategies for controlling bovine trichomoniasis. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guérin (BCG) vaccination induces a type of immune memory known as "trained immunity", characterized by the immunometabolic and epigenetic changes in innate immune cells. However, the molecular mechanism underlying the strategies for inducing and/or boosting trained immunity in alveolar macrophages remains unknown. Here, we found that mucosal vaccination with the recombinant strain rBCGPPE27 significantly augmented the trained immune response in mice, facilitating a superior protective response against Mycobacterium tuberculosis and non-related bacterial reinfection in mice when compared to BCG. Mucosal immunization with rBCGPPE27 enhanced innate cytokine production by alveolar macrophages associated with promoted glycolytic metabolism, typical of trained immunity. Deficiency of the mammalian target of rapamycin complex 2 and hexokinase 1 abolished the immunometabolic and epigenetic rewiring in mouse alveolar macrophages after mucosal rBCGPPE27 vaccination. Most noteworthy, utilizing rBCGPPE27's higher-up trained effects: The single mucosal immunization with rBCGPPE27-adjuvanted coronavirus disease (CoV-2) vaccine raised the rapid development of virus-specific immunoglobulin G antibodies, boosted pseudovirus neutralizing antibodies, and augmented T helper type 1-biased cytokine release by vaccine-specific T cells, compared to BCG/CoV-2 vaccine. These findings revealed that mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via reprogramming mTORC2- and HK-1-mediated aerobic glycolysis, providing new vaccine strategies for improving tuberculosis (TB) or coronavirus variant vaccinations, and targeting innate immunity via mucosal surfaces. [ABSTRACT FROM AUTHOR]

Mycobacterium orygis has been isolated from several cases of tuberculosis in various species of animal in India but documentation of the histopathological lesions caused by this organism is scant. Lung and liver tissues with caseous nodules from cattle (n = 8), lung samples from spotted deer (Axis axis) (n = 5) and lung and mediastinal lymph node samples from buffalo (n = 9) were subjected to histopathology and isolation of Mycobacterium spp. Isolation was carried out using the BACTEC MGIT 960 Automated Mycobacterial Detection System and acid-fast positive cultures were identified to species level using polymerase chain reaction (PCR) employing published primer pairs. Three M. orygis isolates (two from cattle, one from deer) were obtained, whole genome sequenced and the sequences submitted to the National Center for Biotechnology Information Sequence Read Archive. Eight samples (four cattle, one deer and three buffalo) were confirmed as M. orygis positive by PCR. Histopathological examination of the M. orygis -PCR-positive cattle samples revealed acid-fast organisms in lung sections along with macrophages, epithelioid cells, lymphocytes and Langhans giant cells. Granuloma stages I to IV were seen in the cattle and buffalo samples and stage III in the spotted deer sample. This report is the first description of the gross and histopathological lesions of tuberculosis caused by M. orygis in buffalo and documents the gross and histopathological findings of M. orygis tuberculosis in cattle and deer. [ABSTRACT FROM AUTHOR]

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Tuberculosis (TB), as one of the leading causes of death, poses a serious predicament to the world. MicroRNAs (miRNAs) play a role in the post-transcriptional regulation of gene expression. It has been reported that the expression of miRNAs changes upon mycobacterial infection; the screening and identification of miRNAs regulating the expression of genes could benefit our understanding of TB pathogenesis and generate effective strategies for its control and prevention. In this study, luciferase assays showed that miR-4687-5p is bound to the 3′-untranslated region of natural resistance-associated macrophage protein 1 (NRAMP1). Additionally, we found a significant increase in miR-4687-5p expression in Mycobacterium tuberculosis (Mtb)-infected A549 cells. Concomitantly, we detected a reduced level of NRAMP1 expression, suggesting that NRAMP1 is one of the targets of miR-4687-5p. Infection experiments evidenced that the transfection of miR-4687-5p induced a decrease in NRAMP1 expression and increased intracellular Mtb loads post-infection, indicating that miR-4687-5p promotes the intracellular survival of Mtb through its downregulation of the NRAMP1 protein level. We also found that the transfection of miR-4687-5p induced increased apoptosis and decreased cell proliferation post-infection with Mtb. The results presented in our study suggest that miR-4687-5p may be indicative of the susceptibility of Mtb infection to humans and could act as a potential therapeutic target for tuberculosis treatment. [ABSTRACT FROM AUTHOR]

Objective: The main objective was to know the current situation of livestock production, problems and potentialities, in the municipalities of Matías Romero, Santa María Petapa and San Juan Guichicovi, Oaxaca, located in the transoceanic corridor of the Isthmus of Tehuantepec. Design/methodology/approach: The diagnosis was made in eight communities in the municipalities of Matías Romero, Santa María Petapa and San Juan Guichicovi, located north of the Isthmus of Tehuantepec region, Oaxaca. To determine the sample size, the formula suggested by (Snedecor and Cochran, 1967 and Rojas, 1979) was used. It indicates that the elements must be selected through a random draw with replacement, to define the population, the list of production units registered in the Ministry of Agriculture and Rural Development, whose universe is 215, from which, a sample of 41 units was taken. Results: 36% of the interviewees indicated that the ownership of their land is ejidal, 34% is communal and 30% is small property. The interviewed livestock producers develop their livestock activities on an average of 37 hectares. The production units with the smallest area are 8.5 hectares and those with the largest area are 140 hectares. Of the total number of interviewees, 78% provide themselves with water for cattle in the pasture or corrals, coming from rivers and streams, other sources are springs with 12% and dams with 10%. It is considered that the characteristics described provide adequate conditions for livestock. A problem that afflicts livestock in the tropics in the presence of Ixodoida spp, in addition to other types of Mites, the options and alternatives to combat the tick in the PRODETER territory are through the bathroom, regularly it is done by using spray backpack, also the use of Pour on (loin) and tick-killing baths. The misuse of tick control products has generated resistance and problems for farmers (Piña et al., 2017). More than half of the farmers do not participate in animal health campaigns, only 36% do participate. The animal health campaigns in which farmers participate in PRODETER are bovine tuberculosis and paralytic rabies, 24% respectively, tick control 20% and finally brucellosis with 16%. Leos-Rodríguez, (2008) in the work of economic and productive characterization of bovine cattle producers that make up the list of PROGAN beneficiaries in Mexico, observed that the percentage of producers that participated in campaigns against ticks, tuberculosis and brucellosis is above 91%. What is superior to what was found in this diagnosis. Limitations on study/implications: One of the main limitations was that the PRODETER Program was financed by the State for one year only and with that, in the first instance, it limited the intervention to see the effects and levels of adoption of the technological model in the Family Production Units. Findings/conclusions: There is ignorance in the use of food supplements, so the development of calves, and the milk production and fertility of the cows, do not express the potential due to the lack of the necessary nutrients in the different productive stages. There is little use of the rangelands because the farmers ignore the practices to give maintenance, make divisions in the paddocks, so they do not rotate. Among the problems detected, the following stand out, among others: the lack of training, the lack of availability of technicians or experts to attend them, the cost of artificial insemination technology and the long periods between births, which causes calf production to decrease. Therefore, the lack of training in artificial insemination, stallion evaluation and crossbreeding systems for genetic improvement, limit the development of livestock with better quality standards in the region of the Isthmus of Tehuantepec, Oaxaca. The diagnosis as such provides elements for the territorial development of livestock in the transoceanic corridor, since it offers areas of opportunity throughout the production process and can satisfactorily help livestock in that region. [ABSTRACT FROM AUTHOR]

The myosin heavy chain 3 (MYH3) gene is an essential gene that affects muscle development. This study aimed to discuss the expression characteristics of the MYH3 gene and its effect on the proliferation and differentiation of bovine myoblasts. Quantitative real time-PCR results display that the expression level of MYH3 was higher in muscle tissue, and the expression increased in the early stage of myoblast differentiation. Interfering with the MYH3 gene in myoblasts resulted in fewer EDU-positive cells and decreased expression of proliferation marker genes. Interference with MYH3 can also affect the differentiation process of myoblasts. Regarding phenotype, myotube differentiation in the interference group was slowed or even stopped. Interference with the expression of MYH3 could significantly reduce the expression of myogenic differentiation marker genes. The above results show that MYH3 is mainly expressed in muscle tissue and is highly expressed in the early stage of differentiation of bovine myoblasts, and interfering with the MYH3 can promote the proliferation and inhibit the differentiation of bovine myoblasts. This study provides a theoretical basis for revealing the regulatory process of bovine myoblast proliferation and differentiation and bovine molecular breeding. [ABSTRACT FROM AUTHOR]

Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guérin (BCG); this may reflect the inability of intradermal vaccination to optimally induce pulmonary immunity. In contrast, respiratory Mycobacterium tuberculosis infection usually results in the immune-mediated bacillary containment of latent tuberculosis infection (LTBI). Here we present RNA-Seq-based assessments of systemic and pulmonary immune cells from LTBI participants and recipients of intradermal and oral BCG. LTBI individuals uniquely display ongoing immune activation and robust CD4 T cell recall responses in blood and lung. Intradermal BCG is associated with robust systemic immunity but only limited pulmonary immunity. Conversely, oral BCG induces limited systemic immunity but distinct pulmonary responses including enhanced inflammasome activation potentially associated with mucosal-associated invariant T cells. Further, IL-9 is identified as a component of systemic immunity in LTBI and intradermal BCG, and pulmonary immunity following oral BCG. The ability of BCG vaccination to prevent pulmonary tuberculosis could be improved by targeting mucosal immunity within the lung. Here the authors compare latent Mtb-infected donors with intradermal or oral BCG vaccine recipients to show distinct systemic and pulmonary immune responses are induced by differing routes of natural infection or vaccination. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis has evolved several mechanisms to counter host defense arsenals for its proliferation. Here we report that M. tuberculosis employs a multi-pronged approach to modify host epigenetic machinery for its survival. It secretes methyltransferase (MTase) Rv2067c into macrophages, trimethylating histone H3K79 in a non-nucleosomal context. Rv2067c downregulates host MTase DOT1L, decreasing DOT1L-mediated nucleosomally added H3K79me3 mark on pro-inflammatory response genes. Consequent inhibition of caspase-8-dependent apoptosis and enhancement of RIPK3-mediated necrosis results in increased pathogenesis. In parallel, Rv2067c enhances the expression of SESTRIN3, NLRC3, and TMTC1, enabling the pathogen to overcome host inflammatory and oxidative responses. We provide the structural basis for differential methylation of H3K79 by Rv2067c and DOT1L. The structures of Rv2067c and DOT1L explain how their action on H3K79 is spatially and temporally separated, enabling Rv2067c to effectively intercept the host epigenetic circuit and downstream signaling. Singh et al. show how the M. tuberculosis methyltransferase Rv2067c outsmarts host epigenetic machinery by methylating histone H3 prior to its assembly into nucleosomes, thereby ensuring the pathogen's intracellular survival/success. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a zoonotic disease that can spread from animals to humans as well as from human to human. Little research has been conducted on bovine tuberculosis prevalence and molecular characterization in the western part of Ethiopia. To investigate this, a cross-sectional study was conducted on slaughtered cattle at the Nekemte municipal abattoir between January 2020 and June 2021. A detailed postmortem examination, culture, acid-fast staining technique, molecular characterization using RD4 deletion, and spoligotyping were all carried out. Based on a detailed postmortem examination, the overall prevalence of bovine tuberculosis was 7.8% (80 of 1020). Mycobacterium isolation confirmed only 12.5% (10/80) of the suspected tuberculosis tissue lesions. With acid-fast bacilli staining, all Mycobacterium spp. isolates (n = 10) were positive. However, only 9/10 isolates were confirmed to be M. bovis with RD4 molecular deletion typing. Spoligotyping revealed that 55.6% (5/9) of the isolate patterns had previously been reported, but 44.4% (4/9) of the isolates were new. In the current investigation, it was discovered that 80% (4/5) of the M. bovis strains circulating in the cattle population of study regions were SB2233 (2/5) and SB0134 (2/5), whereas 20% (1/5) of the strains corresponded to SB1176, which is compatible with previously documented M. bovis spoligotypes. These findings suggested that M. bovis was the main cause of bovine tuberculosis in the study area and posed a risk of disease transmission from cattle to humans due to low levels of public health awareness. As such, improved awareness among citizens and the development of control policies are warranted. [ABSTRACT FROM AUTHOR]

The Protein- O -mannosyltransferase is crucial for the virulence of Mycobacterium tuberculosis , the etiological agent of tuberculosis. This enzyme, called MtPMT (Rv1002c), is responsible for the post-translational O -mannosylation of mycobacterial proteins. It catalyzes the transfer of a single mannose residue from a polyprenol phospho-mannosyl lipidic donor to the hydroxyl groups of selected Ser/Thr residues in acceptor proteins during their translocation across the membrane. Previously, we provided evidence that the loss of MtPMT activity causes the absence of mannoproteins in Mycobacterium tuberculosis , severely impacting its intracellular growth, as well as a strong attenuation of its pathogenicity in immunocompromised mice. Therefore, it is of interest to develop specific inhibitors of this enzyme to better understand mycobacterial infectious diseases. Here we report the development of a "target-based" phenotypic assay for this enzyme, assessing its O -mannosyltransferase activity in bacteria , in the non-pathogenic Mycobacterium smegmatis strain. Robustness of the quantitative contribution of this assay was evaluated by intact protein mass spectrometry, using a panel of control strains, overexpressing the MtPMT gene, carrying different key point-mutations. Then, screening of a limited library of 30 compounds rationally chosen allowed us to identify 2 compounds containing pyrrole analogous rings, as significant inhibitors of MtPMT activity, affecting neither the growth of the mycobacterium nor its secretion of mannoproteins. These molecular cores could therefore serve as scaffold for the design of new pharmaceutical agents that could improve treatment of mycobacterial diseases. We report here the implementation of a miniaturized phenotypic activity assay for a glycosyltransferase of the C superfamily. [ABSTRACT FROM AUTHOR]

Wildlife populations may be the subject of management interventions for disease control that can have unintended, counterproductive effects. Social structure exerts a strong influence over infectious disease transmission in addition to other characteristics of populations such as size and density that are the primary target for disease control. Social network approaches have been widely used to understand disease transmission in wildlife but rarely in the context of perturbations, such as culling, despite the likely impacts of such disturbance on social structure and disease dynamics.Here we present a 'removal' study of a free‐living population of resident Canada geese Branta canadensis, a highly social species that is frequently managed by culling and can carry pathogens relevant to human and domestic animal health. We quantified social network structure and spatial behaviour before and after controlled culling of individuals during the summer moult.Culling did not substantially increase individual social connectivity. Individuals that moulted at cull sites or were formerly strongly associated with removed birds were more likely to strengthen and maintain any surviving existing associations while also forming new associations. However, the establishment of new associations was largely compensatory (with only small increases in the number and strength of connections) and occurred locally.Synthesis and applications: Geese that survived the cull responded by strengthening existing social relationships and forming new, compensatory relationships with birds local to them in the network. In the short term, such compensatory adjustments to patterns of association in response to culling could facilitate pathogen transmission. But in the longer term, controlled culling of geese is unlikely to strongly influence pathogen spread and may even slow transmission into new social clusters by reducing wider mixing. When managing wildlife for disease control, in addition to changes in social network structure the prevalence of infection at the time of the cull and the mode of transmission (e.g. direct vs. environmental) will also be critical determinants of disease transmission risk in perturbed populations of geese and other wild animals. [ABSTRACT FROM AUTHOR]

A cross-sectional study was conducted on 500 grazing cattle under a pastoral production system in the southern zone of Nasarawa state, North-Central Nigeria to determine the prevalence and risk factors associated with bovine tuberculosis using a Single intradermal Comparative Tuberculin Test (SCITT) from April 2019 to February 2020. The total number of animals with bTB was 46 (9.2%) and the results were significantly higher in older animals between 5-6years (OR: 7.4; CI: 1.54-35.4; P=0.000) and in those animals that were = 7 years (OR: 5.7; CI: 1.24-25-9; P=0.00) old and likely at risk of having more bTB. Additionally, the prevalence was significantly higher in female animals (OR:3.7; CI:1.5-8.8; p=0.003), also a significant prevalence was observed as the herd size increased from 31-80 (OR:1.95; CI:0.75-5.0; p=0.000) as well as from 81-171 (OR:5.5; CI: 2.14-14.4; p=0.000). Moreso, the prevalence was significant with the location of the animals, as areas with grazing reserves appeared to have more odds and more likely to have bTB: Awe (OR:9.6; C I:.2-4.4); Doma (OR:6.9; I:1.5-30.1; p= 0.01); Keana (OR:4.5; CI:0.96-21.6; p=0.01); Obi (OR:3.5; CI:0.7-17; p=0.01). The major risk factors for bovine tuberculosis in this study were sex, age, herd size, and location, contributing largely to the spread of bTB in the study area. [ABSTRACT FROM AUTHOR]

Simple Summary: Campylobacter fetus subsp. venerealis (Cfv) is the causative agent of bovine genital campylobacteriosis (BGC), also known as bovine venereal campylobacteriosis, which is a disease relevant to international trade listed by the World Organization for Animal Health (WOAH). In Germany, BCG was already found to be endemic in the 1920s, shortly after the agent and the disease had been described for the first time. It can be assumed that BCG had already circulated uncontrolled for a long time in the predecessor states of Germany, influenced only by the political situation and trading networks of the time. A single genetic Cfv lineage was identified which probably emerged in the 19th century and diversified over time. Interestingly, no recurrent cross-border introduction became evident. Recent ambitious efforts of German agricultural policies made for animal welfare, conservation of environment and genetic resources and necessary structural adjustment must go hand in hand with control measures of veterinary public health. This review gives insight into the history of bovine genital campylobacteriosis considering the structural change in cattle farming in Germany and reflecting on the political background of the time. Contagious bovine genital campylobacteriosis (BGC), also known as bovine venereal campylobacteriosis, is a disease relevant to international trade listed by the World Organization for Animal Health (WOAH). It is caused by Campylobacter fetus subsp. venerealis (Cfv), one of three subspecies of Campylobacter fetus. Bulls are the reservoir but BGC may also be spread by artificial insemination (AI). BGC is characterized by severe reproductive losses such as infertility, early embryonic death and abortion with considerable economic losses. This significant economic impact has prompted several countries to adopt stringent eradication and surveillance measures to contain the disease. While there are commercial and autologous vaccines available, scientific evidence for the effectiveness of vaccination is still lacking. In Germany, BCG was already found to be endemic in the 1920s, shortly after the agent and the disease had been described for the first time. It can be assumed that BCG had already circulated uncontrolled for a long time in the predecessor states of Germany, influenced only by the political situation and trading networks of the time. After WW II, BCG was eradicated in the German Democratic Republic due to industrialized cattle production based on AI but it was still endemic at low levels in the Federal Republic of Germany with its diverse cattle production. There has been a steady decline in BGC incidence in re-unified Germany over the past 28 years. A single genetic Cfv lineage was identified which probably emerged in the 19th century and diversified over time. Interestingly, no recurrent cross-border introduction became evident. This review gives insight into the history of bovine genital campylobacteriosis considering the structural change in cattle farming in Germany and reflecting on the political background of the time. [ABSTRACT FROM AUTHOR]

In this article, we consider modeling arbitrarily censored survival data with spatio‐temporal covariates. We demonstrate that under the piecewise constant hazard function, the likelihood for uncensored or right‐censored subjects is proportional to the likelihood of multiple conditionally independent Poisson random variables. To address left‐ or interval‐censored subjects, we propose to impute the exact event times and convert them into uncensored subjects, enabling the application of the integrated nested Laplace approximation to update model parameters using the imputed data. We introduce an iterative algorithm that alternates between imputing event times for left‐ and interval‐censored subjects and re‐estimating model parameters. The proposed method is assessed through a simulation study and applied to analyze a spatio‐temporal survival dataset in a wildlife disease study investigating bovine tuberculosis in white‐tailed deer in Michigan. [ABSTRACT FROM AUTHOR]

The bacillus Calmette–Guérin (BCG) is an attenuated bacterium derived from virulent Mycobacterium bovis. It is the only licensed vaccine used for preventing severe forms of tuberculosis in children. Besides its specific effects against tuberculosis, BCG administration is also associated with beneficial non-specific effects (NSEs) following heterologous stimuli in humans and mice. The NSEs from BCG could be related to both adaptive and innate immune responses. The latter is also known as trained immunity (TI), a recently described biological feature of innate cells that enables functional improvement based on metabolic and epigenetic reprogramming. Currently, the mechanisms related to BCG-mediated TI are the focus of intense research, but many gaps are still in need of elucidation. This review discusses the present understanding of TI induced by BCG, exploring signaling pathways that are crucial to a trained phenotype in hematopoietic stem cells and monocytes/macrophages lineage. It focuses on BCG-mediated TI mechanisms, including the metabolic-epigenetic axis and the inflammasome pathway in these cells against intracellular pathogens. Moreover, this study explores the TI in different immune cell types, its ability to protect against various intracellular infections, and the integration of trained innate memory with adaptive memory to shape next-generation vaccines. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guérin (BCG) Danish strain 1331 (CattleBCG) is currently the lead vaccine candidate for the control of bovine tuberculosis (TB) in cattle in GB, where prior vaccination has shown to result in a significant reduction in bovine TB pathology induced by infection with Mycobacterium bovis (M. bovis). A critical knowledge gap in our understanding of CattleBCG is the duration of immunity post vaccination at the minimum intended vaccine dose. To this end, we performed an experiment where calves were vaccinated with a targeted dose of 106 CFU and, after a period of 52 weeks, experimentally infected with M. bovis. Post mortem examination performed 13 weeks after infection revealed a statistically significant reduction in the severity of TB pathology in the CattleBCG vaccinated group compared with the unvaccinated control group. Additionally, this study allowed us to further assess the diagnostic performance of a defined antigen DIVA reagent (DST-F) developed to detect infected amongst vaccinated animals. Our results demonstrate that when used in a skin test format, DST-F showed high specificity (100 %) in BCG-vaccinated animals when tested prior to infection, whilst detecting all infected animals when re-tested after infection. Furthermore, we also present results supporting the use of the DST-F reagent in an interferon-gamma release assay. In conclusion, the results of this study demonstrate a 52-week duration of immunity following administration of a minimum dose of CattleBCG. This evidence will be a fundamental component in our efforts to apply for UK marketing authorisation to enable vaccination of cattle as a significant additional control measure in the ongoing fight against bovine TB in GB. [ABSTRACT FROM AUTHOR]

Bovine respiratory disease (BRD) is a significant health issue in the North American feedlot industry, causing substantial financial losses due to morbidity and mortality. A lack of effective vaccines against BRD pathogens has resulted in antibiotics primarily being used for BRD prevention. The aim of this study was to develop a mucosal vaccine against the BRD pathogen, Mannheimia haemolytica, using Bacillus subtilis spores as an adjuvant. A chimeric protein (MhCP) containing a tandem repeat of neutralizing epitopes from M. haemolytica leukotoxin A (NLKT) and outer membrane protein PlpE was expressed to produce antigen for adsorption to B. subtilis spores. Adsorption was optimized by comparing varying amounts of antigen and spores, as well as different buffer pH and reaction temperatures. Using the optimal adsorption parameters, spore-bound antigen (Spore-MhCP) was prepared and administered to mice via two mucosal routes (intranasal and intragastric), while intramuscular administration of free MhCP and unvaccinated mice were used as positive and negative control treatments, respectively. Intramuscular administration of MhCP elicited the strongest serum IgG response. However, intranasal immunization of Spore-MhCP generated the best secretory IgA-specific response against both PlpE and NLKT in all samples evaluated (bronchoalveolar lavage, saliva, and feces). Since proliferation of M. haemolytica in the respiratory tract is a prerequisite to lung infection, this spore-based vaccine may offer protection in cattle by limiting colonization and subsequent infection, and Spore-MhCP warrants further evaluation in cattle as a mucosal vaccine against M. haemolytica. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is the leading cause of human death worldwide due to Mycobacterium tuberculosis (Mtb) infection. Mtb infection can cause macrophage pyroptosis. PERK, as a signaling pathway protein on the endoplasmic reticulum, plays an important role in infectious diseases. It is not clear whether PERK is involved in the regulation of pyroptosis of macrophages during Mtb infection. In this study, Bacillus Calmette–Guerin (BCG) infection resulted in high expression of pro-caspase-1, caspase-1 p20, GSDMD-N, and p-PERK in the THP-1 macrophage, being downregulated with the pre-treatment of GSK2656157, a PERK inhibitor. In addition, GSK2656157 inhibited the secretion of IL-1β and IL-18, cell content release, and cell membrane rupture, as well as the decline in cell viability induced by BCG infection. Similarly, GSK2656157 treatment downregulated the expressions of pro-caspase-1, caspase-1 p20, caspase-11, IL-1β p17, IL-18 p22, GSDMD, GSDMD-N, and p-PERK, as well as reducing fibrous tissue hyperplasia, inflammatory infiltration, and the bacterial load in the lung tissue of C57BL/6J mice infected with BCG. In conclusion, the inhibition of PERK alleviated pyroptosis induced by BCG infection, which has an effect of resisting infection. [ABSTRACT FROM AUTHOR]

Mycophage endolysins are highly diverse and modular enzymes composed of domains involved in peptidoglycan binding and degradation. Mostly, they are characterized by a three-module design: an N-terminal peptidase domain, a central catalytic domain and a C-terminal peptidoglycan binding domain. Previously, the affinity of cell wall binding domains (CBDs) to the mycobacterial peptidoglycan layer was shown for some of these endolysins. In this study, an in depth screening was performed on twelve mycophage endolysins. The discovered CBDs were characterized for their binding affinity to Mycobacterium (M.) bovis bacille Calmette-Guérin (BCG), a largely unexplored target and an attenuated strain of M. bovis , responsible for bovine tuberculosis. Using homology-based annotation, only four endolysins showed the presence of a known peptidoglycan binding domain, the previously characterized pfam 01471 domain. However, analysis of the secondary structure aided by AlphaFold predictions revealed the presence of a C-terminal domain in the other endolysins. These were hypothesized as new, uncharacterized CBDs. Fusion proteins composed of these domains linked to GFP were constructed and positively assayed for their affinity to M. bovis BCG in a peptidoglycan binding assay. Moreover, two CBDs were able to fluorescently label M. bovis BCG in milk samples, highlighting the potential to further explore their possibility to function as CBD-based diagnostics. • Previously characterized pfam 01471 domain was annotated in mycophage endolysins. • Mycophage endolysins contain new, uncharacterized cell-wall binding domains. • Cell-wall binding domains fused to GFP fluorescently labelled M. bovis BCG in milk. [ABSTRACT FROM AUTHOR]

Simple Summary: The local immune response within the central nervous systems (CNSs) of seven badgers naturally infected with canine distemper virus (CDV) in Asturias (Atlantic Spain) was evaluated via immunohistochemistry. Microglia and astrocytes were the cell types present in the foci of gliosis, whereas T or B lymphocytes were absent. The knowledge gained in the field of the immunopathogenesis of diseases affecting the CNS could clarify CDV disease patterns in badgers. Canine distemper virus (CDV) affects a huge diversity of domestic and wild carnivores, with increasing numbers of mortality events worldwide. The local cell-mediated immune response elicited against a natural infection is an important factor in determining the outcome of CDV infection. Therefore, the purposes of this study were to describe the local immune response within the central nervous systems (CNSs) of seven badgers naturally infected with CDV in Asturias (Atlantic Spain) and to determine the phenotype and distribution of microglial cells, T and B lymphocytes, and astrocytes in the foci of gliosis located in the thalamus and cerebellum using immunohistochemistry. The immunohistochemical assessment demonstrated the presence of Iba1-positive microglia and GFAP-positive astrocytes in the foci of gliosis, whereas T (CD3-negative) or B (CD20-negative) lymphocytes in those same lesions were absent. Our results also revealed that the badgers with natural CDV encephalitis presented lesions mostly located in the white matter of the thalamus and cerebellum, suggesting a CDV-specific tropism for the white matter of badger brains in those locations. The knowledge gained in the field of the immunopathogenesis of distemper disease affecting the CNSs of badgers could help to clarify CDV disease patterns in this species. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of pediatric morbidity and mortality. Young children are at high risk of TB following Mtb exposure, and this vulnerability is secondary to insufficient host immunity during early life. Our primary objective was to compare CD4+ and CD8+ T-cell production of proinflammatory cytokines IFN-gamma, IL-2, and TNF-alpha in response to six mycobacterial antigens and superantigen staphylococcal enterotoxin B (SEB) between Ugandan adults with confirmed TB (n = 41) and young Ugandan children with confirmed (n = 12) and unconfirmed TB (n = 41), as well as non-TB lower respiratory tract infection (n = 39). Flow cytometry was utilized to identify and quantify CD4+ and CD8+ T-cell cytokine production in response to each mycobacterial antigen and SEB. We found that the frequency of CD4+ and CD8+ T-cell production of cytokines in response to SEB was reduced in all pediatric cohorts when compared to adults. However, T-cell responses to Mtb-specific antigens ESAT6 and CFP10 were equivalent between children and adults with confirmed TB. In contrast, cytokine production in response to ESAT6 and CFP10 was limited in children with unconfirmed TB and absent in children with non-TB lower respiratory tract infection. Of the five additional mycobacterial antigens tested, PE3 and PPE15 were broadly recognized regardless of TB disease classification and age. Children with confirmed TB exhibited robust proinflammatory CD4+ and CD8+ T-cell responses to Mtb-specific antigens prior to the initiation of TB treatment. Our findings suggest that adaptive proinflammatory immune responses to Mtb, characterized by T-cell production of IFN-gamma, IL-2, and TNF-alpha, are not impaired during early life. [ABSTRACT FROM AUTHOR]

Many studies have focused on SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) co-infection consequences. However, after a vaccination plan against COVID-19, the cases of severe disease and death are consistently controlled, although cases of asymptomatic and mild COVID-19 still happen together with tuberculosis (TB) cases. Thus, in this context, we sought to compare the T cell response of COVID-19-non-vaccinated and -vaccinated patients with active tuberculosis exposed to SARS-CoV-2 antigens. Flow cytometry was used to analyze activation markers (i.e., CD69 and CD137) and cytokines (IFN-γ, TNFα, IL-17, and IL-10) levels in CD4+ and CD8+ T cells upon exposure to SARS-CoV-2 peptides. The data obtained showed that CD8+ T cells from non-vaccinated TB patients present a high frequency of CD69 and TNF-α after viral challenge compared to vaccinated TB donors. Conversely, CD4+ T cells from vaccinated TB patients show a high frequency of IL-10 after spike peptide stimulus compared to non-vaccinated patients. No differences were observed in the other parameters analyzed. The results suggest that this reduced immune balance in coinfected individuals may have consequences for pathogen control, necessitating further research to understand its impact on clinical outcomes after COVID-19 vaccination in those with concurrent SARS-CoV-2 and Mtb infections. [ABSTRACT FROM AUTHOR]

Copyright of Veterinarska Stanica is the property of Croatian Veterinary Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Therapeutic vaccines have promise as adjunctive treatment for tuberculosis (TB) or as preventives against TB relapse. An important development challenge is the limited understanding of T helper (Th) cell roles during these stages of disease. A murine model of TB relapse was used to identify changes in Th populations and cytokine microenvironment. Active TB promoted expansion of Th1, Th2, Th17, and Th22 cells and cytokines in the lung. Following drug therapy, pulmonary Th17 and Th22 cells contracted, Th1 cells remained elevated, while Th cells producing IL-4 or IL-10 expanded. At relapse, Th22 cells failed to re-expand in the lung despite a moderate re-expansion of Th1 and Th17 cells and an increase in Th cytokine polyfunctionality. The dynamics of Th populations further differed by tissue compartment and disease presentation. These outcomes identify immune bias by Th subpopulations during TB relapse as candidate mechanisms for pathogenesis and targets for therapeutic vaccination. [ABSTRACT FROM AUTHOR]

Background: Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic progressive granulomatous enteritis mainly affecting domestic and wild ruminants worldwide. Although paratuberculosis could be prevail in Ethiopia, there is a scarcity of epidemiological data on paratuberculosis in the country. Thus, this study was conducted to estimate the prevalence of paratuberculosis based on gross and microscopic lesions in cattle slaughtered at ELFORA Abattoir, central Ethiopia. Small intestines and associated lymph nodes of 400 apparently healthy cattle which were slaughtered at ELFORA export abattoir were examined for gross and microscopic lesions of paratuberculosis. The microscopic lesions were classified into four grades (I-IV) based on the type and number of cells infiltrated into the lesion. The prevalence of paratuberculosis was estimated on the basis of gross as well as microscopic lesion of paratuberculosis. Results: The prevalence of paratuberculosis was 11.25% (95% Confidence interval, CI = 0.083–0.148) on the basis of gross lesion. However, relatively lower prevalence (2.0%, 95% CI = 0.01, 0.039) was recorded based on microscopic lesion. The gross lesions were characterized by intestinal thickening, mucosal corrugations and enlargement of associated mesenteric lymph nodes. On the other hand, the microscopic lesions were characterized by granuloma of different grades ranging from grade I to grade III lesions. Conclusions: The present study indicated the occurrence of paratuberculosis in cattle of Ethiopia based on the detection of gross and microscopic lesions consistent with the lesion of paratuberculosis. The result of this study could be used as baseline information for future studies on the epidemiology and economic significance of paratuberculosis. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified host genetic variants associated with paratuberculosis (PTB) susceptibility. Most of the GWAS-identified SNPs are in non-coding regions. Connecting these non-coding variants and downstream affected genes is a challenge and, up to date, only a few functional mutations or expression quantitative loci (cis-eQTLs) associated with PTB susceptibility have been identified. In the current study, the associations between imputed whole-genome sequence genotypes and whole RNA-Sequencing data from peripheral blood (PB) and ileocecal valve (ICV) samples of Spanish Holstein cows (N = 16) were analyzed with TensorQTL. This approach allowed the identification of 88 and 37 cis-eQTLs regulating the expression levels of 90 and 37 genes in PB and ICV samples, respectively (False discorey rate, FDR ≤ 0.05). Next, we applied summary-based data Mendelian randomization (SMR) to integrate the cis-eQTL dataset with GWAS data obtained from a cohort of 813 culled cattle that were classified according to the presence or absence of PTB-associated histopathological lesions in gut tissues. After multiple testing corrections (FDR ≤ 0.05), we identified two novel cis-eQTLs affecting the expression of the early growth response factor 4 (EGR4) and the bovine neuroblastoma breakpoint family member 6-like protein isoform 2 (MGC134040) that showed pleiotropic associations with the presence of multifocal and diffuse lesions in gut tissues; P = 0.002 and P = 0.017, respectively. While EGR4 acts as a brake on T-cell proliferation and cytokine production through interaction with the nuclear factor Kappa β (NF-κß), MGC134040 is a target gene of NF-κß. Our findings provide a better understanding of the genetic factors influencing PTB outcomes, confirm that the multifocal lesions are localized/confined lesions that have different underlying host genetics than the diffuse lesions, and highlight regulatory SNPs and regulated-gene targets to design future functional studies. [ABSTRACT FROM AUTHOR]

Background Bovine Tuberculosis is a respiratory disease caused by the pathogen Mycobacterium bovis (M. bovis) that infects cattle. Though rare, this disease can also affect humans, as well as domestic and wild animals, making it a serious concern. Therefore, searching for alternative and new vaccines with high efficiency and safety is the main goal in bovine tuberculosis prophylaxis. New vaccines, known as vector vaccines, have the potential to become safe and effective alternatives to the traditional BCG vaccine. In this study, two major immunodominant proteins of M. bovis Esat-6 and TB10.4 were utilized to create a vector vaccine for bovine tuberculosis. Methods The Esat-6 and TB10.4 genes were amplified by PCR. The amplified and purified PCR products were sequenced by the Sanger method. Assembly and multiple alignments of amplicon nucleotides were carried out in the MEGA 11 software. Result Two genes of the local strain 0078-M. bovis-8/RIBSP were sequenced. The nucleotide sequences were deposited in the GenBank database. Comparative analysis of the nucleotide sequences of the ESAT-6 and TB10.4 genes established 100% identity of the compared strains of Mycobacterium. Conclusion Through the use of phylogenetic analysis, it has been confirmed that the amplified genes are related to the mycobacteria genus. This discovery allows the development of a vector vaccine against bovine tuberculosis utilising these genes. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the 'iron-tropic' Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the 'iron-tropic' Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings. [ABSTRACT FROM AUTHOR]

Serological assays for bovine tuberculosis diagnosis require the use of multiple Mycobacterium bovis specific antigens to ensure the detection of infected animals. In the present study, identification and selection process of antigens, based on data from published proteomic studies and involving the use of bioinformatics tools and an immuno-screening step, was firstly performed for identifying novel antigens that elicit an antibody response in M. bovis infection. Based on this approach, a panel of 10 M. bovis antigens [with known relevance (MPB70, MPB83, MPB70/83, and ESAT6/CFP10) and novel (Mb1961c, Mb1301c, Mb3871, Mb1403, Mb0592, and PE25/PPE41)] were constructed and thenused to develop a new multiplexed serological assay based on Luminex technology. The performance of the Luminex-bTB immunoassay was evaluated using sera from cattle with known tuberculosis status. Among the proteins whose ability to detect bovine tuberculosis was evaluated for the first time, PE25/PPE41 and Mb1403, but not Mb3871, showed good detection capacity. Following multiple antigen combination, the final Luminex-bTB immunoassay included seven antigens (MPB70, MPB83, MPB70/83, ESAT6/CFP10, PE25/PPE41, Mb1403, and Mb0592) and showed better global performance than the immunoassay using the four usual antigens (MPB70, MPB70/83, MPB83 and ESAT6/CFP10). The specificity and sensitivity values were, respectively, of 97.6% and 42.8% when the cut-off of two-positive antigens was used to classify samples as positive. With the use of the more-restrictive criterion of three-positive antigens, the specificity increased to 99.2% but the sensitivity decreased to 23.9%. The analysis of antigen profiles generated with the Luminex-bTB immunoassay showed that mainly serodominant proteins were recognized in samples from infected cattle. The detection of Mb1961c and Mb1301c appeared to be associated with presumed false-positive results. Moreover, sera from cattle originating from bTB-outbreaks but having inconclusive or negative skin test results were identified as positive by the Luminex-bTB immunoassay and showed an antigen pattern associated with M. bovis infection. The Luminex-bTB immunoassay including seven antigens may be useful as adjunct test for the detection of M. bovis–infected herds, and different cut-offs could be applied according to the bovine tuberculosis epidemiological context. [ABSTRACT FROM AUTHOR]