Search Results (15,284)

C-type lectin receptors (CLRs) play central roles in sensing fungal pathogens and coordinating Syk-CARD9-dependent inflammatory responses. While Dectin-3 contributes to antifungal immunity against several clinically relevant fungi, its role in host defense against Paracoccidioides brasiliensis remains unknown. Here, we investigated the impact of Dectin-3 deficiency using Clec4d⁻/⁻ mice and primary phagocytes during experimental Paracoccidioidomycosis. Dectin-3-deficient macrophages and dendritic cells displayed unaltered cytokine production, phagocytic capacity, fungicidal activity, and maturation following P. brasiliensis challenge. Consistently, the absence of Dectin-3 did not impact survival or pulmonary fungal burden during long-term systemic infection. These findings are consistent with functional redundancy among CLRs, potentially involving Dectin-1, Dectin-2, or other Syk-coupled receptors rendering Dectin 3 dispensable for immunity to systemic experimental P. brasiliensis infection. Full article

Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), remains a leading cause of skin and soft tissue infections (SSTIs) worldwide. Patients with renal edema, including those with nephrotic syndrome and chronic kidney disease (CKD), and critical illness, are particularly susceptible because of barrier dysfunction, immune impairment, and altered antimicrobial pharmacokinetics. This narrative review examines the mechanisms linking renal edema to increased susceptibility to cutaneous S. aureus infection and discusses their diagnostic and therapeutic implications. Three interconnected pathophysiological pathways appear central to this susceptibility: disruption of the cutaneous barrier, nephrotic and uremic immune dysfunction, and impaired lymphatic immune surveillance. These abnormalities facilitate bacterial colonization, and invasion, while S. aureus further exploits the renal host through adhesins, toxins, biofilm formation, and immune-evasion mechanisms. The review also highlights the challenges of managing severe staphylococcal infections in patients with kidney disease and critical illness, where augmented renal clearance, expanded volume of distribution, extracorporeal renal support, and fluctuating renal function may substantially influence antimicrobial exposure. Current management requires early recognition, source control, individualized antimicrobial selection, renal-adapted dosing, therapeutic drug monitoring, and antimicrobial stewardship. Although emerging anti-virulence and immunomodulatory strategies show promise, most remain at the preclinical or early translational stage. Overall, renal edema should be regarded as a biologically active modifier of host–pathogen interactions that contributes to increased susceptibility to cutaneous S. aureus infection across the spectrum of kidney disease. Full article

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Coronaviruses are a diverse group of RNA viruses classified into alpha, beta, gamma, and delta genera, with SARS-CoV-2 belonging to the beta-coronavirus family. The virus exhibits high transmissibility and causes a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to severe complications such as acute respiratory distress syndrome, multi-organ failure, and death, particularly among elderly and immunocompromised individuals. Structurally, SARS-CoV-2 possesses a large single-stranded RNA genome encoding major structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, which play critical roles in host-cell recognition and viral infection. Understanding the molecular mechanisms of virus–host interactions, especially protein–protein interactions (PPIs), is essential for uncovering viral pathogenesis and identifying potential therapeutic targets. Traditional experimental techniques for PPI detection, such as yeast two-hybrid and affinity purification methods, are often expensive, labor-intensive, and prone to inaccuracies. Consequently, computational approaches based on machine learning (ML) and deep learning (DL) have gained significant attention for efficient and scalable PPI prediction. These methods use diverse biological information, including protein sequences, structural features, genomic data, Gene Ontology annotations, and interaction networks, to model complex biological relationships. This survey reviews computational approaches to PPI prediction, highlighting ML- and DL-based techniques, methodological advances, performance evaluation practices, and limitations that affect benchmark comparability. It also discusses biological databases and data sources commonly used in PPI studies and explicitly considers how models trained in coronavirus-centered settings may generalize to other viral families with different mechanisms of host interaction. Full article

The concurrent circulation of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unveiled complex host–pathogen interactions governed by temporal dynamics of innate immune activation. This narrative review synthesizes evidence from human air–liquid interface (ALI) epithelial models, animal studies (hamster, ferret), clinical cohorts, and randomized controlled trials (2015–2026) to delineate the molecular mechanisms underlying viral interference between these two major respiratory pathogens. Prior IAV infection induces a robust type I/III interferon (IFN) response and broad interferon-stimulated gene (ISG) upregulation that restricts subsequent SARS-CoV-2 replication within a critical 24–72 h temporal window. Conversely, SARS-CoV-2 employs a multi-layered immune evasion strategy that blunts IFN induction, providing minimal heterologous protection. Simultaneous co-infection tends to exacerbate disease severity. Host genetic determinants, including OAS1 and TLR7 variants, modulate interference capacity. Therapeutically, early pegylated IFN-λ shows clinical benefit, while experimental evidence from in vitro and animal models suggests oseltamivir may paradoxically reduce IAV-induced interference. These findings underscore the need for multi-pathogen diagnostics, temporally informed clinical decision-making, and IFN-based therapeutic strategies during co-circulation periods. Full article

Trematodes are a class of parasitic flatworms with complex life cycles involving multiple hosts. They can influence the physiology and behavior of their intermediate hosts to improve the efficiency of transmission to definitive hosts, including by increasing host mortality. However, the mechanisms of their effect on the crustacean nervous system leading to neuronal dysregulation and its consequences have not been sufficiently elucidated. This study investigated the effects of infection by metacercariae of the trematode Cercaria fluviocinguli on the serotonin (5-HT) immunoreactivity, inflammation, and pathological processes in the nervous system of the shore crab Hemigrapsus sanguineus. The regions in the brain, the ventral nerve cords (VNC), and the nerves targeted by this parasite were examined by immunohistochemistry and confocal laser scanning microscopy methods. The cysts and the enclosed flukes caused compaction, compression, and distortion of many nerve fibers of the VNC and also impaired conduction in the mixed nerves of the thoracic ganglia controlling locomotion. The infection by C. fluviocinguli induced a decrease in 5-HT-like immunoreactivity in neurons and neuropils of the VNC, damage to nerve fibers and neurons of the VNC, inflammatory reactions, and apoptosis. In heavily infected crabs, the increased content of TUNEL-positive cells in the VNC was correlated with granuloma accumulation. Further investigations into host–parasite interaction mechanisms under controlled experimental conditions are needed to clarify the actual effects of encapsulated and non-encapsulated metacercariae on host behavior and their role in transmission to the next host. Full article

Chronic atrophic gastritis (CAG) is a pivotal precancerous condition in gastric carcinogenesis, with progression typically following the classic Correa cascade. Although Helicobacter pylori (H. pylori) infection is widely recognized as the principal etiological factor, the persistence of gastric cancer (GC) risk in a subset of patients after successful eradication suggests that gastric microbiota dysbiosis may also contribute to CAG progression. In recent years, high-throughput sequencing technologies have revealed distinct microbial restructuring in patients with CAG, characterized by decreased microbial diversity, depletion of commensal taxa, and enrichment of opportunistic pathogens. These compositional changes are accompanied by metabolic dysfunction, activation of inflammatory signaling pathways, and disruption of immune homeostasis, which may contribute to a microenvironment permissive for precancerous transformation of the gastric mucosa. Probiotics and related microbiome-based therapeutics, including prebiotics, synbiotics, and postbiotics, have emerged as promising adjunctive strategies for H. pylori eradication and disease management. Their beneficial effects are mediated through multiple mechanisms, including remodeling of the microbial community, inhibition of pathogen colonization, modulation of host immune responses, and restoration of mucosal barrier integrity. However, whether these interventions can reverse established atrophic or metaplastic lesions remains unclear. In addition, how strain specificity, dose dependency, and interindividual heterogeneity influence clinical efficacy has yet to be fully elucidated. In this review, we summarize the compositional and functional features of gastric microbiota dysbiosis in patients with CAG, as well as the mechanisms and clinical applications of microbiome-based interventions. We further highlight current limitations in the field and discuss future directions for precision microecological therapies integrating multi-omics approaches, engineered probiotics, and artificial intelligence. These advances may provide a theoretical framework and practical guidance for the diagnosis and management of CAG and the prevention of GC. Full article

Background: Cutibacterium avidum is an emerging opportunistic pathogen responsible for device-associated infections, including prosthetic joint and breast implant infections. Unlike its relative C. acnes, for which phage therapy has been explored, C. avidum infections are recalcitrant to antibiotics, and no infecting bacteriophages have been described to date. Here, we report the isolation and characterization of ΦCA1NRNZ, to the best of our knowledge, the first lytic phage described against C. avidum. Methods: ΦCA1NRNZ was obtained from wastewater sampling at the Sorek Treatment Facility in Jerusalem. Wastewater metagenomics, transmission electron microscopy, genome sequencing, host-range testing, efficiency of plating (EOP), aerobic and anaerobic lysis assays, and antibiofilm assays against mature C. avidum biofilms were performed. Results: Metagenomic analysis indicated low and transient detection of C. avidum-classified reads in wastewater. ΦCA1NRNZ was identified as a long-tailed Caudoviricetes with a ~320 nm virion. Its 33,712 bp dsDNA genome (GenBank PV441878.1) encodes 46 predicted proteins, shares 76.5% nucleotide identity with C. acnes phage ΦFD1, and contains divergent tail-fiber and host-recognition genes. No known bacterial virulence, toxin, human pathogenicity-associated, or antibiotic-resistance genes were identified. ΦCA1NRNZ lysed all 11 clinical C. avidum isolates tested under aerobic and anaerobic conditions, with EOP values of 0.11–5.55, mean 1.87, and showed no lytic activity against 25 C. acnes isolates. Against mature biofilms, ΦCA1NRNZ reduced total biomass by 28.4% (p = 0.014), reduced viable cell counts by approximately two logs, and increased extracellular ATP release (p < 0.001). Conclusions: The strict species specificity and significant in vitro antibiofilm activity of ΦCA1NRNZ support its potential for phage therapy of device-associated C. avidum infections. Full article

Equids, primarily horses, are mostly used for recreational purposes, although in some rural areas they also serve as working animals, maintaining close and frequent contact with humans. Their risk of exposure to vector-borne and zoonotic pathogens can be affected by host-related factors, management practices and environmental conditions. This study aimed to investigate the seroprevalence and associated risk factors for infections by Babesia caballi, Toxoplasma gondii, Coxiella burnetii, and Borrelia burgdorferi sensu lato in equids from Southwestern Greece. A total of 159 equids were tested using commercial serological assays. Weighted prevalence estimates were applied to account for unequal sampling. Associations were assessed using chi-square tests and logistic regression. Ecological niche modelling was employed to evaluate geographic patterns and environmental correlates. Seroprevalence was highest for B. caballi (8.81%), followed by T. gondii (7.55%) and C. burnetii (1.26%). No seropositive animals were detected for B. burgdorferi sensu lato. Ecological niche modelling showed acceptable predictive performance for B. caballi, with BIO14 and BIO6 emerging as the main environmental predictors. In contrast, the T. gondii model exhibited unacceptable predictive performance, and its environmental associations should therefore be interpreted cautiously. Complementary Random Forest analyses yielded comparable environmental rankings but showed higher classification performance for T. gondii than for B. caballi. Overall, the findings contribute to understanding pathogen exposure patterns in equids and underscore the importance of integrating epidemiological and environmental data in surveillance efforts. Full article

Retroviruses induce immunosuppression in their infected hosts. This phenomenon is well described for the immunodeficiency viruses, with human immunodeficiency virus type 1 (HIV-1) representing the best-studied example, but it also occurs in other retroviral infections. Immunosuppressive properties were first characterized in murine leukemia viruses (MuLV). Additional well-studied examples include feline leukemia virus (FeLV) and koala retrovirus (KoRV). Investigations into the mechanisms underlying retrovirus-induced immunosuppression revealed that not only inactivated viral particles but also their purified transmembrane (TM) envelope proteins exhibit immunosuppressive activity. However, in certain retroviral infections, additional viral proteins contribute to the immunosuppression in vivo. Within the TM envelope proteins, a highly conserved region—designated the immunosuppressive (isu) domain—was identified. Synthetic peptides corresponding to this domain suppress a wide range of in vitro immune responses, possibly by regulating Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR pathways. They modulate cytokine release and alter gene expression in immune cells, mirroring the activity of the corresponding TM envelope protein. Mutations in the sequence abrogate the effect. Numerous TM envelope proteins have demonstrated immunosuppressive activity in vivo in a tumor rejection model, and mutations within the isu domain also abrogate this function. These studies have important implications for reproduction, particularly through the immunosuppressive syncytins in the placenta, for tumor development, where similar mechanisms may protect cancer cells from the host immune system, and for vaccine development and xenotransplantation. Notably, immunization with TM envelope proteins carrying mutations in the isu domain elicits stronger immune responses compared with the wild-type proteins. Finally, the potential of retroviral TM envelope proteins to protect xenotransplants from immune rejection will be discussed. Full article

Avian influenza viruses (AIVs) are widely distributed and have a wide range of hosts. Recently, the number of cases of infection associated with the circulation of highly pathogenic avian influenza H5N1 2.3.4.4b has raised concerns about its high transmission capacity in birds and mammals. This study analyzed swabs from bird and mammal species from the coast of Paraná and the northwest region of São Paulo, Brazil, for the presence of AIV in animals that did not present clinical or histopathological lesions of infection that indicated the need for molecular characterization during monitoring. Of the 661 animals analyzed, three tested positive, two of which were birds (Sula leucogaster and Thalasseus acuflavidus) while one was a mammal (Otaria flavescens) (0.45%, CI 95%: 0.16–1.33). A complete genome sequence of H5N1 AIV was obtained from a brown booby (Sula leucogaster) from the Paraná coast (GISAID accession number: EPI_ISL_1897537). Our study reinforces the importance of continuous genomic surveillance, especially in AIV hosts that do not show signs of infection, to enhance the One-Health assessment approach. Full article

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein–Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical “second hit” when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a “tumor of malaria survivors,” peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies. Full article

Background/Objectives: The coccidian protozoan Toxoplasma gondii (T. gondii) is among the most prevalent zoonotic parasites worldwide. Nitric oxide (NO) production by macrophages is considered a critical microbicidal mechanism against various intracellular pathogens, including T. gondii. While the role of the inducible nitric oxide synthase isoenzyme (iNOS) has been widely investigated in both acute and chronic T. gondii infections, the specific functions of the neuronal (nNOS) isotype in the antiparasitic immune response, particularly during chronic toxoplasmosis, remain largely uncovered. Hence, this report seeks to bridge the gap regarding the potential participation of nNOS in experimental chronic T. gondii infection. Methods: The study included 56 Swiss albino mice, equally allocated into four experimental groups: (G1) negative control, (G2) infected control, (G3) infected-L-arginine-treated, and (G4) infected-7-Nitroindazole-treated. All groups except (G1) were orally infected with the avirulent (ME49) T. gondii strain. Nine weeks post-infection, all mice were euthanized for parasitological, histopathological, immunohistochemical, and biochemical analyses. Results: The NO donor, L-arginine, induced a significant reduction in the number of T. gondii cysts, together with strong nNOS immunoreactivity in the brain sections of the treated mice. Conversely, the highest parasitic burden was observed following selective nNOS inhibition with 7-Nitroindazole, exacerbating parasite-induced pathology. Conclusions: The neuronal isotype serves as a critical source of NO production during the chronic stage of T. gondii infection, thereby enhancing parasite elimination and contributing to host tissue protection. Full article

Canine vector-borne pathogens (CVBPs) pose a major challenge in shelter medicine, yet data from shelter populations in Vietnam remain unknown. This study determined the prevalence, and risk factors of CVBPs in shelter dogs in northern Vietnam. Blood samples from 300 apparently healthy dogs from three shelters in Hanoi were screened by PCR for Babesia vogeli, Hepatozoon canis, Rickettsia spp., and Mycoplasma spp. Representative positive amplicons underwent Sanger sequencing and BLAST analysis. Sequence analysis showed 96.07–100% identity with reference strains, with phylogenetic trees confirming clustering within B. vogeli, H. canis, M. haemocanis and R. felis clades. Overall, 43.7% (131/300) of dogs were infected with at least one pathogen, with shelter-level prevalence ranging from 38.0 to 52.0%. Single infections accounted for 35.0%, dominated by R. felis (25.7%) and M. haemocanis (24.0%), B. vogeli and H. canis were low (1.3% each). Co-infections were found in 8.7% of dogs, primarily R. felis and M. haemocanis (8.3%). No evaluated host factors (age, sex, breed, body size, housing style) significantly associated with infection (p > 0.05). This study provides the first molecular evidence of canine vector-borne pathogen circulation in Vietnamese shelter dogs, emphasizing the need of ectoparasite control and One Health-oriented surveillance. Full article

Ilyonectria is a common soil-inhabiting fungal genus that comprises numerous plant phytopathogenic species capable of infecting a wide array of crops, medicinal herbs, and horticultural plants. However, the lack of a reliable and efficient genetic transformation method has severely hindered the elucidation of the pathogenic mechanisms of Ilyonectria pathogens. In this study, we established an efficient protoplast-mediated genetic transformation method for two dominant Panax root rot pathogens, I. robusta and I. vredehoekensis. Key parameters governing high-quality protoplast preparation, including mycelium culture time, enzyme composition, osmotic stabilizer type, digestion speed, and digestion time, were systematically optimized. Subsequently, orthogonal experiments were conducted to optimize the PEG-CaCl₂-mediated transformation conditions and to screen regeneration media for protoplasts. The optimal enzymatic system is composed of 20 mg/mL driselase and 10 mg/mL lysing enzyme, with 0.7 M NaCl as the osmotic stabilizer. Under these conditions, high-viability and high-quality protoplasts were obtained from I. vredehoekensis after 3 h of digestion at 150 rpm, and from I. robusta after 2 h of digestion at 100 rpm, yielding 5.52 × 10⁷ CFU/mL and 5.75 × 10⁷ CFU/mL protoplasts, respectively. Efficient transformation was achieved using a mannitol-prepared STC buffer mediated by 40% PEG4000. PCR and fluorescence microscopy verified positive transformants. Additionally, pathogenicity assays showed no significant differences in virulence between the transformed and wild-type strains, suggesting that the transformation procedure did not alter virulence. To the best of our knowledge, this is the first study to successfully establish genetic transformation methods for I. robusta and I. vredehoekensis, providing an essential technical platform for functional gene analysis, pathogenicity studies, and host–pathogen interaction research. In addition, the optimized transformation strategy may serve as a valuable reference for studies on other Ilyonectria species. Full article

Outbreaks of avian infectious bronchitis virus (IBV) often occur in vaccinated flocks. The antibody-dependent enhancement (ADE) has been proposed as a potential mechanism underlying coronavirus vaccine failure. However, this hypothesis has yet to be substantiated in flocks. This study demonstrates ADE occurrence in IBV (gamacoronavirus) in vitro and in vivo. Using the SPF chicken host model, primary infection with an O-glycosylation-modified attenuated strain enhanced pathogenesis upon secondary homologous/heterologous virulent challenge, increasing morbidity/mortality (≥30%), pathological lesions, and viral loads. Notably, sequentially attenuated infections also induced ADE, suggesting live attenuated vaccine risks. The immune serum raised against the O-glycosylation-modified attenuated strain was also pre-mixed with the challenge strain, and the mixtures were then inoculated into target cells, non-susceptible macrophage cells, or a co-culture of both cell types. The serum-virus complexes replicated poorly in macrophages, yet immune cells amplified the expression of inflammatory factors and ADE-mediated viral replication in target cells, indicating a significant promoting role of immune cells in this process. The concentrations of complement component C3 and neutralizing antibodies in the immune serum were also measured, and results showed that the induction of this ADE is associated with high complement component C3 and low neutralizing antibody titers. These findings highlight risks for vaccines and antibody-based therapeutic strategies of coronavirus infection. Full article