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Multidrug-resistant , a prevalent opportunistic pathogen in hospitals, presents a substantial risk to immunocompromised patients, triggering life-threatening conditions including pneumonia, bacteremia, and sepsis, which can be fatal. Therefore, it is urgent to develop new therapeutic strategies to combat and eradicate multidrug-resistant infection. Our finding reveals that promotes the mice treated with 5-fluorouracil (5-FU) to defend against multidrug-resistant infection via the mTORC1-IFN-I signaling pathway. Mechanistically, triggers mTORC1 activation through the phosphorylation of p38 MAPK, and mTORC1 is required for the subsequent activation of IFN-I signaling pathways in response to treatment. studies have demonstrated that enhances the clearance of in mice subjected to 5-FU chemotherapy, with this effect being mediated through the mTORC1 signaling pathway. Our study provides insight into the therapeutic intervention of enhancing IFN-I signaling and boosting host defense against bacterial infections via the administration of .
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http://dx.doi.org/10.1016/j.bbrep.2025.102213 | DOI Listing |
Cell Biochem Biophys
September 2025
Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34003, Türkiye, Turkey.
Vitamin B12 is a vital water-soluble vitamin containing a central cobalt atom within its corrin ring structure. It exists in several derivatives, among which methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl) are the biologically active forms that serve as cofactors in essential enzymatic reactions. Although the neurological and hematological consequences of vitamin B12 deficiency have been extensively studied, its role in immune regulation remains less well understood.
View Article and Find Full Text PDFJ Exp Med
November 2025
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Host-pathogen interactions involve two critical strategies: resistance, whereby hosts clear invading microbes, and tolerance, whereby hosts carry high pathogen burden asymptomatically. Here, we investigate mechanisms by which Salmonella-superspreader (SSP) hosts maintain an asymptomatic state during chronic infection. We found that regulatory T cells (Tregs) are essential for this disease-tolerant state, limiting intestinal immunopathology and enabling SSP hosts to thrive, while facilitating Salmonella transmission.
View Article and Find Full Text PDFHeredity (Edinb)
September 2025
Department of Ecology, Environment and Plant Sciences, Stockholm University, Stockholm, 10691, Sweden.
Parasitoid wasps are major causes of mortality of many species, making host immune defences a common target of adaptive evolution, though such targets outside model species are poorly understood. In this study, we used two tests of positive selection to compare across three closely related Galerucella leaf beetles that show substantial differences in their phenotypic response to the shared parasitoid wasp Asecodes parviclava, their main natural enemy. Using a codon-based test, which detects excess amino acid fixations per locus along each species' lineage, we found more evidence of positive selection on parasitoid-relevant immune genes in the species with the strongest immunocompetence (G.
View Article and Find Full Text PDFPLoS Pathog
September 2025
Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China.
The exocyst complex is a heterooctameric protein complex, the individual components of the complex are thought to act on specific biological processes. However, the role of Sec10, the central subunit of the complex, in host defense and viral replication remains unclear. Here, we reported that Sec10 significantly impairs the activation of JAK-STAT signal pathway of type I IFN (IFN-I) response against both DNA- and RNA-viruses, and promotes viral replication, respectively.
View Article and Find Full Text PDFPLoS Pathog
September 2025
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
SUMO-modified Tripartite Motif Protein 28 (TRIM28; KAP1) plays a crucial role in repressing endogenous retroelement (ERE) transcription. We previously provided evidence that loss of SUMO-modified TRIM28 triggered by influenza A virus (IAV) infection promotes activation of host antiviral immunity via a mechanism involving derepression of EREs and production of immunostimulatory RNAs. While the IAV NS1 protein might limit consequences of such activation via its dsRNA-binding activity, we hypothesized that other human pathogenic viruses could have evolved more direct strategies to counteract this potential ERE-based defense system.
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