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Plastic waste has emerged as a major environmental concern in recent years. As plastic waste discharged into the marine environment, it undergoes a breakdown process, eventually accumulating in aquatic organisms in the form of microplastics (MPs). To date, reduced food intake, nutritional absorption, and impaired immune system are known adverse effects of MPs-exposed aquatic organisms. This study aims to investigate whether MP exposure accelerated white spot syndrome virus (WSSV) infection in Pacific white shrimp (Penaeus vannamei) via laboratory tests. Briefly, experimental shrimp were divided into four groups; WSSV (group 1); MP (group 2); WSSV + MP (group 3); and Control (group 4). No mortality was observed in group 2, group 4, and even in group 1. However, group 3 showed a cumulative mortality of 50% during the experimental period. The PCR assay results showed no WSSV in the other three groups (groups 1, 2, and 4), but the dead and alive shrimp collected from group 3 were confirmed to be infected with the virus. Histopathological examination revealed normal structures in the hepatopancreas, gill, and muscle tissues of group 4, whereas numerous abnormally shaped nuclei were detected in the gill tissue of group 2. Moreover, group 1 showed minor WSSV-related lesions with few basophilic inclusion bodies in the gills, interestingly, group 3 exhibited severe lesions with numerous basophilic inclusion bodies in the gills. In conclusion, this study confirmed the correlation between the viral disease of shrimp and MPs, which can cause significant economic losses to the shrimp aquaculture industry.
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The gut microbial and metabolic characteristics of intestinal Behçet's disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn's disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases.
Assuntos
Síndrome de Behçet , Microbioma Gastrointestinal , Metaboloma , Humanos , Síndrome de Behçet/microbiologia , Síndrome de Behçet/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Doença de Crohn/microbiologia , Doença de Crohn/metabolismo , Metabolômica/métodos , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/metabolismo , Biomarcadores , Fezes/microbiologia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/metabolismo , Estudos de Casos e ControlesRESUMO
The increasing economic losses associated with growth retardation caused by Enterocytozoon hepatopenaei (EHP), a microsporidian parasite infecting penaeid shrimp, require effective monitoring. The internal transcribed spacer (ITS)-1 region, the non-coding region of ribosomal clusters between 18S and 5.8S rRNA genes, is widely used in phylogenetic studies due to its high variability. In this study, the ITS-1 region sequence (~600-bp) of EHP was first identified, and primers for a polymerase chain reaction (PCR) assay targeting that sequence were designed. A newly developed nested-PCR method successfully detected the EHP in various shrimp (Penaeus vannamei and P. monodon) and related samples, including water and feces collected from Indonesia, Thailand, South Korea, India, and Malaysia. The primers did not cross-react with other hosts and pathogens, and this PCR assay is more sensitive than existing PCR detection methods targeting the small subunit ribosomal RNA (SSU rRNA) and spore wall protein (SWP) genes. Phylogenetic analysis based on the ITS-1 sequences indicated that the Indonesian strain was distinct (86.2% nucleotide sequence identity) from other strains collected from Thailand and South Korea, and also showed the internal diversity among Thailand (N = 7, divided into four branches) and South Korean (N = 5, divided into two branches) samples. The results revealed the ability of the ITS-1 region to determine the genetic diversity of EHP from different geographical origins.
Assuntos
DNA Espaçador Ribossômico , Enterocytozoon , Microsporidiose , Penaeidae , Filogenia , Reação em Cadeia da Polimerase , Enterocytozoon/genética , Enterocytozoon/isolamento & purificação , Enterocytozoon/classificação , Penaeidae/microbiologia , Penaeidae/parasitologia , Animais , DNA Espaçador Ribossômico/genética , Reação em Cadeia da Polimerase/métodos , Microsporidiose/microbiologia , Microsporidiose/diagnóstico , DNA Fúngico/genética , Primers do DNA/genética , Fezes/microbiologia , Fezes/parasitologia , Análise de Sequência de DNA , TailândiaRESUMO
The intricate role of innate type-2 cytokines in immune responses is increasingly acknowledged for its dual nature, encompassing both protective and pathogenic dimensions. Ranging from defense against parasitic infections to contributing to inflammatory diseases like asthma, fibrosis, and obesity, these cytokines intricately engage with various innate immune cells. This review meticulously explores the cellular origins of innate type-2 cytokines and their intricate interactions, shedding light on factors that amplify the innate type-2 response, including TSLP, IL-25, and IL-33. Recent advancements in therapeutic strategies, specifically the utilization of biologics targeting pivotal cytokines (IL-4, IL-5, and IL-13), are discussed, offering insights into both challenges and opportunities. Acknowledging the pivotal role of innate type-2 cytokines in orchestrating immune responses positions them as promising therapeutic targets. The evolving landscape of research and development in this field not only propels immunological knowledge forward but also holds the promise of more effective treatments in the future.
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Recently identified human FOXP3lowCD45RA- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (Tregs). In spite of their implication in tumors, the mechanism for generation of FOXP3lowCD45RA- INS cells in vivo is unclear. We showed that the FOXP3lowCD45RA- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3lowINS-Tregs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3lowINS-Tregs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3lowINS-Tregs including FOXP3lowCD45RA- cells that promote antitumor immunity.
Assuntos
Proteínas de Ligação à Região de Interação com a Matriz , Doenças Mitocondriais , Neoplasias , Humanos , Camundongos , Animais , Linfócitos T Reguladores , Ácidos Cetoglutáricos/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Citocinas/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismoRESUMO
Influenza viruses escape immunity owing to rapid antigenic evolution, which requires vaccination strategies that allow for broadly protective antibody responses. We found that the lipid globotriaosylceramide (Gb3) expressed on germinal center (GC) B cells is essential for the production of high-affinity antibodies. Mechanistically, Gb3 bound and disengaged CD19 from its chaperone CD81, permitting CD19 to translocate to the B cell receptor complex to trigger signaling. Moreover, Gb3 regulated major histocompatibility complex class II expression to increase diversity of T follicular helper and GC B cells reactive with subdominant epitopes. In influenza infection, elevating Gb3, either endogenously or exogenously, promoted broadly reactive antibody responses and cross-protection. These data demonstrate that Gb3 determines the affinity and breadth of B cell immunity and has potential as a vaccine adjuvant.
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Anticorpos Antivirais , Linfócitos B , Centro Germinativo , Infecções por Orthomyxoviridae , Orthomyxoviridae , Triexosilceramidas , Formação de Anticorpos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Centro Germinativo/efeitos dos fármacos , Centro Germinativo/imunologia , Triexosilceramidas/metabolismo , Triexosilceramidas/farmacologia , Animais , Camundongos , Camundongos Knockout , Humanos , Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologiaRESUMO
Tumors develop strategies to evade immunity by suppressing antigen presentation. In this work, we show that prosaposin (pSAP) drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor dendritic cells (DCs) leads to cancer immune escape. We found that lysosomal pSAP and its single-saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, transforming growth factor-ß (TGF-ß) induced hyperglycosylation of pSAP and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. pSAP hyperglycosylation was also observed in tumor-associated DCs from melanoma patients, and reconstitution with pSAP rescued activation of tumor-infiltrating T cells. Targeting DCs with recombinant pSAP triggered tumor protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of pSAP in tumor immunity and may support its role in immunotherapy.
Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Saposinas , Evasão Tumoral , Humanos , Células Dendríticas/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Saposinas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Glicosilação , Imunoterapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Apresentação de Antígeno , Linfócitos T CD8-Positivos/imunologiaRESUMO
Background: Notably, 5-aminosalicylates (5-ASA) are vital in treating inflammatory bowel diseases (IBD). The adverse events of 5-ASA rarely occur but they could be fatal. Objectives: We aimed to discover new genetic biomarkers predicting 5-ASA-induced adverse events in patients with IBD. Design: This was a retrospective observational study. Methods: We performed a genome-wide association study on patients with IBD in South Korea. We defined subset 1 as 39 all adverse events and 272 controls; subset 2 as 20 severe adverse events and 291 controls (mild adverse events and control); subset 3 as 20 severe adverse events and 272 controls; and subset 4 as 19 mild adverse events and 272 controls. Logistic regression analysis was performed and commonly found associated genes were determined as candidate single-nucleotide polymorphisms predicting 5-ASA adverse events. Results: Patients with Crohn's disease (CD) were significantly negatively associated with the development of adverse events compared to patients with ulcerative colitis (UC) (5.3% versus 22.9%). However, sex and age at diagnosis were unassociated with the adverse events of 5-ASA. rs13898676 [odds ratio (OR), 20.33; 95% confidence interval (CI), 5.69-72.67; p = 3.57 × e-6], rs12681590 (OR, 7.35; 95% CI, 2.85-19.00; p = 3.78 × e-5), rs10967320 (OR, 4.51; 95% CI, 2.18-9.31; p = 4.72 × e-5), and rs78726924 (OR, 3.54; 95% CI, 1.69-7.40; p = 7.96 × e-5) were genetic biomarkers predicting 5-ASA-induced severe adverse events in patients with IBD. Conclusion: The adverse events of 5-ASA were more common in patients with UC than those with CD in our study. We found that novel rs13898676 nearby WSB2 was the most significant genetic locus contributing to 5-ASA's adverse event risk.