Molecular characterization and expression analysis of the TRAF gene family in the fourfinger threadfin (Eleutheronema tetradactylum).

NETosis in diabetic kidney disease: Molecular mechanisms and therapeutic opportunities.

BackgroundThe increasing prevalence of multidrug-resistant (MDR) bacteria has reduced the effectiveness of standard antibiotics, prompting renewed interest in bacteriophage (phage) therapy as an alternative or adjunctive treatment. Phage therapy offers high specificity, self-amplification at infection sites, and minimal disruption to the gut microbiota. However, clinical implementation is challenging, due to the risk of phage resistance and uncertainties regarding optimal dosing and immune interactions.MethodsPreviously, we demonstrated that a two-phage cocktail exhibited low immunogenicity in mice and, when combined with meropenem, significantly improved clearance of ventilator-associated Pseudomonas aeruginosa pneumonia, reduced inflammation, and disrupted biofilms more effectively than either treatment alone. In the present study, we investigated the interplay between this phage cocktail and innate immune defenses using a murine respiratory infection model and human in vitro assays.ResultsOur findings reveal that the therapeutic efficacy of phage treatment is critically dependent on the presence of neutrophils, which act synergistically with phages to achieve effective bacterial clearance, particularly when bacterial burden exceeds a defined threshold. Alveolar macrophages, however, do not significantly contribute to infection resolution in vivo.ConclusionSince neutrophils play a key-role in supporting phage-mediated Pseudomonas clearance, the efficacy of phage therapy is closely linked to the hosts immune competence – an important consideration when treating immunocompromised patients.

Decoding host immune response: circRNAs in Klebsiella variicola-infected chicken spleens.

Mice have been used as a valuable model for understanding pathophysiological mechanisms of urinary tract infection for almost six decades. Mice offer many advantages including genetic manipulation to test the role of genes and mechanisms, the availability of germ-free mice, and similarities to humans in innate immune defenses and the strain-dependent presence of vesicoureteral reflux. However, like with humans, the mouse bladder urine above the urinary sphincter has generally been assumed to be sterile. Yet, given the presence of urobiomes in other mammals and the emerging role of the human urobiome in the defense of the urinary bladder and upper urinary tract, the existence of a mouse urobiome should be critically examined as indigenous microbiota may influence experimental results. To determine if an indigenous murine urobiome exists, we obtained voided urine from two sets of female C57BL/6J mice during three different intervals using two different extraction and sequencing methods and analyzed them simultaneously by a single method. For one set, we also obtained urine by suprapubic aspiration, which we compared to the paired voided urine samples. We conclude that an indigenous murine urobiome exists and that voided urine contains post-urethral microbes.

RNF34 negatively regulates innate immunity via ubiquitin-mediated TAK1 degradation in miiuy croaker (Miichthysmiiuy).

Background: The extensive use of antibiotics in aquaculture has raised serious concerns, emphasizing the need for sustainable and natural alternatives. This study evaluated the potential of red dragon fruit (Hylocereus polyrhizus) juice by-products (RJB) as a functional feed additive for juvenile red seabream (Pagrus major). Materials and Methods: The bioactive composition and antioxidant capacity of RJB were analyzed, and five experimental diets containing 0, 0.2, 0.4, 0.8, and 1% RJB were fed to fish for 56 days. Results: Growth performance, feed utilization, body composition, antioxidant enzyme activities, and lysozyme activity were evaluated. RJB contained substantial levels of phenolic and flavonoid compounds and exhibited strong radical-scavenging activity. Dietary inclusion of up to 1% RJB did not significantly affect growth, feed efficiency, or plasma biochemistry. However, fish fed the 1% RJB diet showed increased catalase and glutathione levels, significantly enhanced lysozyme activity, and improved survival following Edwardsiella tarda infection. Conclusion: These results demonstrate that RJB can be safely incorporated into marine fish diets to enhance antioxidant capacity and innate immune defense. The valorization of fruit-processing by-products such as RJB offers a promising strategy for developing antibiotic-free and sustainable aquaculture practices.

In vitro evaluation of antiviral and anti-inflammatory activities of selected flavonoids against ISKNV infection in Asian seabass cell line.

Halide binding by myeloperoxidase is regulated by access channel dynamics and charge interactions.

Antimicrobial peptides in crustacean, especially in Procambarus clarkii (crayfish).

Host responses - autophagy, cell death, and inflammation - limit the growth of bacterial pathogens while minimizing tissue damage. During the early stages of infection, Mycobacterium tuberculosis (Mtb) thwarts these and other innate immune defense mechanisms in alveolar macrophages (AMs) derived from the yolk sac; in later stages, it circumvents defenses in recruited mononuclear cells (MNCs) and survives within them despite additional cytokine stimulation from recruited T cells. The mechanisms that drive variable rates of Mtb growth in different macrophage subtypes and how Mtb manipulates inflammatory responses to grow within innate immune cells remain obscure. Here we explored the role of the host factor, Tax-1 binding protein 1 (Tax1bp1), an autophagy receptor that targets pathogens for degradation through selective autophagy and terminates pro-inflammatory cytokine responses. Unexpectedly, we found that Tax1bp1-deficient mice were less susceptible to Mtb infection, and generated reduced inflammatory cytokine responses, compared to wild-type mice; the same mutant mice exhibited decreased growth of, and inflammatory cytokine responses to, Listeria monocytogenes, suggesting that Tax1bp1 plays a role in host responses to multiple intracellular pathogens. Contrary to our previous ex vivo findings in bone marrow-derived macrophages (BMDMs), in vivo growth of Mtb in AMs and a subset of recruited MNCs was more limited in mice lacking Tax1bp1 relative to wild-type mice. To better understand these differences, we performed global protein abundance measurements in mock- and Mtb-infected AM samples ex vivo from wild-type mice. These experiments revealed that Tax1bp1 protein abundance does not significantly change early after infection in AMs but does in BMDMs; moreover, early after infection, Tax1bp1-deficiency reduced necrotic-like cell death -- an outcome that favors Mtb replication -- in AMs but not BMDMs. Together, these results show that deficiency of Tax1bp1 plays a crucial, cell type-specific role in linking the regulation of autophagy, cell death, and anti-inflammatory host responses and overall reducing bacterial growth.

The crosstalk of neutrophil extracellular trap-inflammasome and their roles in disease progression.

The RIG-I-like receptor family of immune proteins.

Drosophila proteasome subunit Rpn8 controls IMD pathway activation via PGRP-SC2 degradation.

Innate immune defense relies on post-translational modifications (PTMs) to protect against viral infections. SUMOylation plays complex roles in viral replication and antiviral defenses in mammals and has been implicated in age-associated diseases. Whether PTMs and SUMOylation contribute to age-induced immunosenescence is unknown. We find that antiviral defense in Caenorhabditis elegans is regulated through SUMOylation of DRH-1, ortholog of the cytosolic pattern recognition receptor RIG-I. The SUMO isopeptidase ULP-4 is essential for deSUMOylation of DRH-1 and activation of the intracellular pathogen response (IPR) after exposure to Orsay virus (OV). ULP-4 stabilizes DRH-1, which translocates to the mitochondria to activate the IPR. Loss of drh-1 or ulp-4 compromises antiviral defense; mutant animals fail to clear OV and develop intestinal pathogenesis. During aging, ulp-4 expression decreases, which promotes DRH-1 proteosomal degradation and IPR loss. Mutating the DRH-1 SUMOylated lysines partially rescued the age-associated lost inducibility of the IPR. Our work establishes that aging results in dysregulated SUMOylation and loss of DRH-1, which compromises antiviral defense and creates a physiological shift to favor chronic pathological infection in older animals.

A mini-review on cathelicidin in fish: Gene expression, immune function, and evolutionary insights.

Regulation of AMPs expression by six Tolls in stomach during WSSV infection in Macrobrachium nipponense.

Neonatal skin: barrier, immunity and infection prevention in the NICU.

Glaesserella parasuis (G. parasuis), a common pathogenic bacterium in the porcine respiratory tract, can cause porcine polyserositis, arthritis, and meningitis. Alveolar macrophages are the first line of defense in the pulmonary innate immunity, and their abnormal apoptosis plays a critical role in the pathogenic process of G. parasuis. Long non-coding RNA maternally expressed gene 3 (MEG3) is associated with G. parasuis infection, but its mechanism remains incompletely unclear. This study aimed to investigate the role of MEG3 in G. parasuis-induced apoptosis of the porcine alveolar macrophage cell line 3D4/21 and its detailed molecular mechanism. Here, we found that MEG3 overexpression promoted G. parasuis-induced apoptosis and upregulated key extrinsic pathway proteins caspase-8 (CASP8) and caspase-3 (CASP3). Mechanistically, MEG3 functioned as a competing endogenous RNA by sponging ssc-miR-135, which directly targets and inhibits CASP8. Consequently, MEG3 overexpression alleviated ssc-miR-135-mediated repression of CASP8. Functional rescue experiments confirmed that either ssc-miR-135 mimic or CASP8 siRNA reversed the pro-apoptotic effect of MEG3. In conclusion, this study reveals that MEG3 relieves the inhibitory effect of ssc-miR-135 on CASP8 through competitively binding, thereby regulating G. parasuis-induced apoptosis of 3D4/21 cells. This study provides new insights into the pathogenic molecular mechanism of G. parasuis.

PANoptosis, a newly defined, multifaceted programmed cell death (PCD) pathway, integrates key features of pyroptosis, apoptosis, and necroptosis. It is orchestrated by multiprotein complexes called PANoptosomes (ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosomes), which assemble via domain interactions in response to specific pathogen- or damage-associated signals. This integrated pathway plays crucial roles in maintaining tissue homeostasis by eliminating infected and damaged cells and provides potent innate immune defence through the coordinated release of inflammatory cytokines and damage-associated molecular patterns (DAMPs), offering superior pathogen clearance compared with single PCD modes. Increasing evidence underscores the significant involvement of PANoptosis in digestive diseases. In gastric cancer, it modulates tumour progression, the immune microenvironment and chemoresistance. PANoptosis drives epithelial cell death in ulcerative colitis and Crohn's disease, contributing to mucosal barrier disruption and inflammation. It influences immune infiltration, metabolic reprogramming, and therapeutic response in colorectal cancer. PANoptosis also contributes to the pathogenesis of diverse liver conditions, including failure, fibrosis, metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma, and mediates pancreatic injury in acute pancreatitis. While research on oesophageal and pancreatic malignancies is nascent, PANoptosis-based molecular subtyping and therapeutic targeting demonstrate translational potential. This review synthesizes current evidence, highlighting PANoptosis as a critical regulator in digestive pathologies and as a promising target for intervention.