Search Results (3,447)

Vibrio tubiashii infection has led to several Babylonia areolata pandemics on the southeast coast of China, yet the immune response of the ivory shell against V. tubiashii and the specific pathogen–host interaction remain unclear. This dynamic study aimed to characterize the response of B. areolata to V. tubiashii infection with the use of pathology, transcriptomics, an enzymatic assay, and inflammatory cytokines. Hepatopancreatic cells showed marked vacuolar degeneration with intact cell membrane and extensive cytoplasmic vacuolization after infection. The dynamic transcriptome of the hepatopancreatic tissue was analyzed by RNA-seq after V. tubiashii infection, and a total of 2733 (3 h), 5610 (24 h), 3323 (48 h), and 418 (72 h) differentially expressed genes (DEGs) were identified during infection. The GO and KEGG analyses showed that the DEGs were enriched in metabolic regulation, lysosome, and multiple immune-related pathways such as the MAPK signaling pathway. The immune response of B. areolata was distinct, where the early stage of immune response (3 h) showed binding, focal adhesion, and apoptosis, as well as an activated antioxidant system. Here, expression of TNF-α, IL-1, and IL-8 was significantly increased in the hepatopancreas, whereas expression of IL-6 and IL-17 increased afterward. During the middle stage (24 h and 48 h), a large number of DEGs were suppressed, especially those associated with metabolism and lysosomes, although their expression returned to normal during prolonged infection (72 h). The PPI network showed that ppp2, atp6, and sos1 were the top immune-related DEGs during infection. Key infection-related and time-course-related genes were analyzed by WGCNA. This study illustrates that oxidative stress, inflammation, and apoptosis are strategies of the hepatopancreatic immune response in B. areolata against V. tubiashii infection and enlightens conservation and production by furthering our understanding of gastropod immunity. Full article

Brucellosis and tuberculosis (TB) are chronic infectious diseases of international public health importance, with developing countries being most affected. The diagnosis of brucellosis and tuberculosis co-infection remains challenging because both diseases present with overlapping nonspecific clinical manifestations, such as prolonged fever, fatigue, and weight loss, and elicit similar cell-mediated immune and inflammatory responses, which can complicate differential diagnosis, particularly in endemic regions. Recently, it has been shown that chronic infections affect cell stress pathways such as oxidative stress and telomere function. The current literature review provides an overview of the relationship between brucellosis and TB at a molecular level, focusing on telomere biology, oxidative stress and the mechanisms of antimicrobial resistance. Due to chronic immune response in brucellosis and TB patients, an increase in reactive oxygen species (ROS) levels is observed, leading to DNA damage and subsequent telomere shortening and alteration of telomerase activity. These alterations might be responsible for immune senescence, weakened defense response and persistent infection. In addition, different methods of drug resistance have been discovered among brucellae and mycobacteria, such as mutation in target sites, efflux systems and intracellular persistence, making their eradication difficult. Finally, the potential role of telomere-related genes and biomarkers of oxidative stress in diagnosis and prognosis is also highlighted. Insights into these interrelated pathways would allow us to have a better understanding of host–pathogen interactions and hence offer a possible means of developing new strategies in the fight against co-infection by finding new biomarkers. Full article

Proteins are the most common targets for antibody discovery and vaccine development, but their sequence variability can limit the breadth of resulting antigens. Lipids represent an alternative class of antigens due to their structural conservation and roles in host–pathogen interactions. Here, we describe the development and optimization of an in vitro antibody selection workflow using lipid-containing nanodiscs as antigen presentation platforms to enable phage and yeast display selections under conditions adapted for these non-protein targets. Lipopolysaccharide (LPS) nanodiscs were first used as a model system to evaluate selection strategies, including competitive and subtractive approaches to reduce non-specific binders, yielding peptide and single-chain variable fragment (scFv) binders that were affinity matured to improve binding signals. The same approach was subsequently used to select scFv antibodies that recognize lipid nanodiscs prepared from Yersinia pestis membrane lipid extracts. These antibodies show binding to lipid nanodiscs derived from Y. pestis, with evidence of selectivity relative to control nanodiscs. Overall, this work establishes a workflow for antibody selection against lipid-containing nanodisc antigens and highlights practical considerations associated with these targets. The approach may be useful for generating affinity reagents to membrane-associated lipids, although further characterization is required to define antigen specificity and functional activity. Full article

Fibropapillomatosis (FP) is a disease that threatens the health and safety of sea turtles globally, with green sea turtles having the highest FP prevalence. FP is associated with Chelonid alphaherpesvirus 5, but the primary etiological agent remains unknown as expression and severity of the virus are influenced by host susceptibility, immunological status, development of epithelial lesions, and environmental factors. This review explores current understanding of FP in green sea turtles, focusing on etiology, pathological features, diagnostic approaches, and rehabilitation strategies. Emphasis is placed on the compounded nature of the disease, integrating factors that influence disease expression. Screening challenges are examined through the limitations of clinical, histological, and molecular methods, particularly in distinguishing latent from active infection. Rehabilitation practices, including surgical intervention and long-term supportive care, are evaluated in the context of treatment outcomes and recurrence risk. Collectively, the evidence supports the interpretation of FP as a disease shaped by host–pathogen–ecology interactions. Improved integration of diagnostic tools and greater focus on natural drivers are essential for advancing understanding of the disease and informing conservation and management efforts. Full article

Uterine infections (metritis and endometritis) are a leading cause of culling and reproductive failure in transition dairy cows, and antibiotic-resistant Gram-negative pathogens limit conventional therapy. This randomized, controlled, multi-farm field trial evaluated whether four intravaginal infusions of a host-adapted lactic acid bacteria (LAB) cocktail (Lactobacillus sakei FUA3089, Pediococcus acidilactici FUA3138, P. acidilactici FUA3140; 10⁸–10⁹ cfu/dose) at −3, −2, +3, and +4 weeks relative to calving reduce periparturient disease and improve milk production. A total of 526 pregnant cows (426 Holstein, 100 Jersey) from four commercial Alberta farms (automatic-milking, parlor, and certified-organic systems) were block-randomized within farm and parity to TRT1 (saline; n = 175), TRT2 (saline + skim milk; n = 176), or TRT3 (LAB cocktail in saline + skim milk; n = 175). Uterine infection incidence was assessed by Metricheck™ mucus scoring and transrectal ultrasonography at +3 and +4 weeks postpartum. Across the principal peripartum infectious outcomes, TRT3 showed a consistent protective effect: uterine infection incidence was lowest in TRT3 (18.8% vs. 25.1% in pooled controls; OR = 0.69; 95% CI, 0.44–1.09; an approximately 25% relative reduction; exact p = 0.12), and this metritis signal was additionally supported by a repeated-measures mixed model accounting for farm, parity, and week (p = 0.0175), although the Bonferroni-adjusted pairwise contrasts were tendencies (adjusted p ≈ 0.12), and the effect did not differ by parity (treatment × lactation interaction, p = 0.97). Subclinical mastitis was numerically lower in TRT3 than in pooled controls (5.3% vs. 8.9%; OR = 0.57; 95% CI, 0.27–1.24; exact p = 0.16), whereas retained placenta, milk fever, displaced abomasum, and lameness showed no clear cow-level treatment effect in the cow-level exact analyses. Milk yield increased significantly in multiparous cows, which produced 4.6 L/day more milk than TRT1 and 3.22 L/day more than TRT2 over the first 50 days in milk (p < 0.01 for both contrasts; treatment × parity interaction, p = 0.01). No effect was seen on milk composition, uterine involution, or reproductive performance. The trial supports intravaginal LAB as a candidate antibiotic-free prophylactic whose response depends on farm- and cow-level contexts and whose mechanisms require confirmation through microbiological and metabolic measurements. Full article

Environmental stressors such as poor water quality, overstocking, and temperature spikes force shrimp to divert energy from growth and immunity to maintain homeostasis, increasing their susceptibility to opportunistic pathogens. Despite this risk, information on how these conditions affect viral and bacterial abundance, diversity, and community structure in shrimp farms remains scarce. To address this gap, this study offers a broad metagenomic analysis of the viral and bacterial communities in a shrimp farm, uncovering their diversity and ecological significance. In total, 13,572 viral operational taxonomic units (vOTUs) were recovered. Most viruses belonged to the realm Duplodnaviria, with Caudoviricetes dominating the libraries. Additionally, some contigs were linked to the Iridoviridae, a family that can affect fish and shrimp. Taken together, these findings highlight the critical role of virus–host interactions in marine environments and underscore the utility of metagenomic analysis for monitoring and safeguarding aquaculture health. Full article

Ticks are haematophagous ectoparasites and vectors of a diverse range of pathogens, exerting substantial impacts on wildlife, domestic animals and public health. In Australia, despite the country’s rich and unique biodiversity, a comprehensive understanding of ticks and tick-borne pathogens associated with wildlife remains limited. Environmental change, urban expansion and climate variability are increasingly disrupting wildlife habitats, potentially intensifying interactions between wildlife hosts, ticks and humans. A broad evidence synthesis of studies published between January 1940 and March 2024 was conducted, retrieving 133 eligible records from Web of Science, CABI Abstracts and PubMed databases. Fifty tick species parasitising 160 wildlife species were identified, predominantly from the genera Ixodes, Amblyomma and Haemaphysalis. The most commonly reported hosts included marsupials, particularly bandicoots, wallabies and possums, with notable tick species being Ixodes tasmani, Ixodes holocyclus and Amblyomma triguttatum. Microorganism records were relatively limited and mostly represented molecular detections or reported associations, including Babesia, Borrelia, Coxiella, Rickettsia and Theileria species, rather than confirmed vector competence, reservoir status or pathogenicity. Key limitations included geographic sampling biases towards eastern Australia, limited molecular identification of ticks and infrequent pathogen screening, particularly regarding the ecology, epidemiology and molecular diversity of host–vector–microorganism interactions. Improved surveillance, expanded molecular characterisation, and integrated One Health investigations are required to better understand the ecological and public health significance of these host–vector–microorganism interactions. Full article

Background/Objectives: West Nile virus (WNV) remains a significant threat to human health, with no approved antiviral treatments or vaccine available. A better understanding of the molecular mechanisms governing flavivirus–host interactions is needed to identify host regulatory pathways involved in infection. This study aimed to investigate how WNV infection remodels the host miRNA–mRNA regulatory landscape. Methods: WNV-induced changes in host miRNA expression in HEK-293 cells were profiled using miRNA-Seq. Transcriptome-wide host gene expression changes in WNV-infected cells were analysed using RNA-Seq. Gene Ontology and pathway enrichment analyses were conducted using DAVID. Integrated miRNA–mRNA network reconstruction was performed using Cytoscape based on the experimentally validated miRNA–mRNA interactions in miRNet database. Results: WNV infection induced global changes in host miRNA expression, with pathogenic NY99 and non-pathogenic Kunjin strains of the virus producing overlapping and strain-specific alterations in the miRNA landscape. Transcriptome analysis showed strong induction of interferon-related responses and activation of NF-κB and MAPK signalling pathways in the infected cells. In contrast, pathways associated with RNA processing, splicing, and proteasomal degradation were downregulated. Integrated miRNA–mRNA network analysis identified miR-197-3p, miR-301b-3p, miR-129-3p, miR-3662, and miR-128-5p as candidate regulatory hubs involved in WNV-induced transcriptome remodelling. These networks suggested that miRNA-mediated regulation may influence antiviral signalling, apoptosis, and RNA metabolism during infection. Conclusions: These findings suggest that WNV infection broadly remodels host miRNA–mRNA regulatory networks and identifies candidate miRNAs that may contribute to the regulation of antiviral and cellular stress responses. These predicted regulatory interactions provide a foundation for future experimental validation. Full article

Phytopathogenic fungi pose a constant threat to worldwide agricultural production. Given the widespread development of fungicide resistance and increasing environmental and regulatory constraints, precision disease-control strategies are urgently needed to enhance selectivity, durability, and sustainability. This review critically examines recent advances in targeted fungicide discovery against phytopathogenic fungi. We categorize these strategies into three complementary groups: (1) targeting fungal biological processes that are essential or infection-associated; (2) disarming pathogen virulence by interfering with immune evasion and effector-mediated interactions; and (3) activating or redirecting host defence through host-directed or dual-action interventions. We compare these strategies with respect to mechanistic rationale, expected selectivity, resistance risk, and field-deployment challenges. Additionally, we discuss emerging enabling technologies—including compound repurposing, structural biology, and artificial intelligence-assisted fungicide design—that accelerate target identification and lead optimization. These strategies have begun to facilitate the discovery of compounds with improved specificity and disease-control potential. We believe that the integrated application of these approaches may support the development of more selective and potentially durable disease-control agents. Full article

Physiologically produced circulating β-amyloid (Aβ) exerts critical physiological functions. Although Aβ is a key player in Alzheimer’s disease (AD), it may initially be beneficial at the onset of infection. As an evolutionary conserved antimicrobial peptide (AMP), Aβ contributes to innate immune defense against pathogens. Host defense peptides such as Aβ and human cathelicidin (LL-37) not only kill pathogens through their antimicrobial activity but also exhibit high affinity for bacterial lipopolysaccharides (LPSs) and membrane receptors. LL-37, which is upregulated in the brain, binds to Aβ, modulating its aggregation; Aβ and LL-37 are protective under physiological conditions, but during chronic infection or dysregulation, their interaction becomes toxic and contributes to AD pathology. Similarly to Aβ, LL-37 can induce neuroinflammation by stimulating human microglia to release inflammatory cytokines, such as TNF-α and IL-6. Neuroinflammation is essential for protecting the brain from pathogens—when prolonged, it drives pathological processes underlying AD, Parkinson’s disease (PD), and other neurodegenerative disorders. Full article

Phytophthora blight, caused by the oomycete pathogen Phytophthora capsici, is a devastating disease that severely constrains pepper (Capsicum annuum) production, leading to significant yield reduction and quality deterioration. Pathogen infection elicits a host immune response that involves extensive transcriptional reprogramming, during which transcription factors (TFs) act as key regulatory hubs linking upstream signaling cascades to downstream defense gene expression networks. NAC TFs represent a plant-specific gene family and play crucial roles in plant growth, development, and response to various stresses. However, the infection-responsive transcriptional dynamics and functions of NAC TFs during pepper–P. capsici interactions remain poorly elucidated. In this study, transcriptome profiling and RT-qPCR analysis of pepper plants challenged with P. capsici identified three NAC TF genes—CaNAC61, CaNAC79, and CaNAC92—that were consistently upregulated at the infection stages. Subcellular localization assays demonstrated that all these three proteins localize to the nucleus. Silencing of CaNAC61, CaNAC79, or CaNAC92 in pepper conferred enhanced resistance to P. capsici. In contrast, their transient overexpression in pepper leaves significantly promoted lesion expansion and suppressed transcript levels of the defense marker genes CaPR1, CaDEF1, and CaLOX1. Consistently, heterologous overexpression in transgenic Nicotiana benthamiana further validated CaNAC61, CaNAC79, and CaNAC92 as negative regulators in resistance to P. capsici. Collectively, our findings demonstrated that CaNAC61, CaNAC79, and CaNAC92 negatively regulate plant resistance to P. capsici, expanding the functional diversity of NAC TFs in plant immune responses and providing valuable candidate targets for genetic improvement against Phytophthora blight. Full article

C-type lectins (CTLs) are proteins with carbohydrate-recognition domains. These macromolecules interact with pathogen components, thereby playing important roles in the immune system. Current studies indicate that silkworm CTLs are involved in Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Nevertheless, the molecular mechanisms through which these CTLs affect viral infection remain unclear. In this study, B. mori C-type lectin 16 (BmCTL16) was identified in the silkworm. Its expression was significantly downregulated upon BmNPV infection. Functional assays showed that BmCTL16 overexpression suppressed BmNPV proliferation, whereas its knockdown enhanced BmNPV proliferation. Protein–protein interaction assays confirmed that BmCTL16 interacts with BmNPV protein Bm9 in the cytoplasm. Notably, BmCTL16 promoted the degradation of Bm9 via the ubiquitin–proteasome system. Knockdown of Bm9 by siRNA significantly reduced BmNPV proliferation, confirming that Bm9 is the key target for BmCTL16 to exert its antiviral function. Collectively, this study reveals a novel CTL-mediated antiviral mechanism. BmCTL16 interacts with Bm9 and promotes its ubiquitin–proteasome degradation, thereby inhibiting viral proliferation. Furthermore, BmNPV evades this host defense by downregulating BmCTL16 expression. These findings enhance our understanding of silkworm CTL-mediated antiviral defense and offer novel perspectives on host–virus interactions in B. mori. Full article

Feline leishmaniosis (FeL) caused by Leishmania infantum is increasingly recognized in endemic areas, but factors influencing susceptibility in cats remain incompletely understood. Because blood group antigens may modulate host–pathogen interactions, this study evaluated whether feline AB blood system phenotypes are associated with L. infantum seropositivity and/or molecular positivity in cats from Italy. Exploratory analyses further assessed whether blood phenotype was associated with the magnitude of indirect fluorescent antibody test (IFAT) antibody titres or with real-time PCR (qPCR) parasite load. In this retrospective cross-sectional study, cats were classified as L. infantum-positive when they had an IFAT titre ≥1:80 and/or a positive qPCR on blood or lymph node aspirates. Feline AB blood typing was performed by tube agglutination, with type B and AB samples confirmed by immunochromatographic testing and back typing. A total of 706 cats were included. Overall, 67/706 cats (9.5%) were classified as L. infantum-positive. Blood phenotype distribution was 83.1% type A, 10.1% type B, and 6.8% type AB. L. infantum positivity was detected in all three phenotypes, and no evidence of association was found between blood phenotype and L. infantum positivity, IFAT seropositivity, qPCR positivity, IFAT titre, or qPCR parasite load. After adjustment for region, blood phenotype remained not significantly associated with L. infantum positivity. These findings suggest that feline AB blood system phenotypes were not associated with L. infantum infection in this feline cohort. Future studies should investigate whether blood phenotype may influence other aspects of FeL, such as clinical expression or disease outcome. Full article

Bovine endometritis remains one of the most significant postpartum uterine disorders. It impairs uterine recovery, compromises fertility, and causes substantial economic losses in dairy production. Growing evidence suggests that the disease cannot be attributed solely to postpartum bacterial contamination; rather, it should be understood as a multifactorial failure to restore uterine homeostasis after calving. This review summarises the latest research findings on six interconnected aspects: the clinical significance of postpartum uterine disease; the diagnostic and biological differences between clinical and subclinical endometritis; the role of microbes in the uterus in health and disease; interactions between the host and uterine bacteria; the mechanisms of persistent inflammatory regulation; and current as well as emerging treatment strategies. Current evidence indicates that postpartum uterine disease is more strongly associated with dysbiosis, reduced microbial diversity, and disturbed microbial succession than with the presence of any single pathogen. Disease progression is driven by complex interplay among microbial ligands, epithelial and stromal immune responses, virulence-associated tissue injury, endocrine disruption, and impaired inflammatory resolution. Furthermore, persistent uterine inflammation is regulated by multilayered networks involving cytokines, prostaglandins, noncoding RNAs, extracellular vesicles, metabolic remodeling, and oxidative stress. Although conventional therapies remain relevant in certain clinical cases, microbiota-oriented approaches, particularly probiotic interventions, have emerged as promising adjunctive strategies for the prevention and control of the condition. Overall, bovine endometritis should be viewed as a disorder caused by disrupted interactions between the host, microbiota and inflammation. Future progress will depend on longitudinal, strain-resolved, and function-oriented studies to enable more precise and less antimicrobial-dependent interventions for postpartum uterine health. Full article

The innate immune response is a critical defense mechanism by which vertebrates recognize and eliminate invading pathogens. Pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns and activate downstream signaling pathways. NOD1, a classic PRR of the NLR family, recruits the adaptor protein RIPK2 to initiate antibacterial signaling. In this study, we cloned and characterized the NOD1 gene from snakehead (Channa argus). Briefly, the full-length NOD1 cDNA is 2829 bp encoding 943 amino acids, showing high homology with Perciformes. The qPCR analysis revealed widespread NOD1 gene expression in various tissues, with significant upregulation in the gill (p < 0.05) and spleen (p < 0.05) following bacterial infection. Overexpression of the NOD1 gene activated the NF-κB signaling pathway in a dose- and time-dependent manner, and specifically responded to the bacterial ligand iE-DAP but not to other tested ligands. Furthermore, NOD1 synergized with the downstream adaptor RIPK2 to enhance NF-κB activity, and direct protein interaction between NOD1 and RIPK2 was confirmed by co-immunoprecipitation. Taken together, these findings demonstrate that snakehead NOD1 plays a critical role in the host antimicrobial immune response. Full article