Project description:This study will evaluate the safety and tolerability of a personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD) treatment in adults with metastatic colorectal cancer.
Project description:Tgr5 is a membrane-bound bile acid receptor that negatively regulates immune cells, although the molecular mechanisms behind this observation remain elusive. Here we report that Tgr5 is upregulated in macrophages during stimulation with Listeria monocytogenes and that Tgr5-deficient macrophages are hyperinflammatory and mice with myeloid Tgr5 deficiency are more susceptible to Listeria monocytogenes sepsis. Unexpectedly, Tgr5-deficient macrophages show reduced glycolysis and ATP citrate lyase expression, which cumulates in Acetyl-CoA deficiency and metabolic-epigenetic gene silencing, driving macrophages towards a hyperinflammatory phenotype during bacterial sepsis
Project description:Several Toll-like receptors are activated by Listeria monocytogenes infection, resulting in the activation of MyD88 dependent signaling pathway. However, the negative role of MyD88 in gene expresson is unclear. To address this, we performed microarray analysis of mRNAs from WT or MyD88-/- peritoneal macrophages infected with Listeria monocytogenes.
Project description:DNA damage response kinase ATM regulates the genetic program of lymphocytes with phsiologically induced DNA DSBs. In bone marrow-derived macrophages, related kinase DNAPKcs is also responsible for activating DNA damage responses after infection with Listeria monocytogenes. Here we show that both ATM and DNA-PKcs regulate the genetic program of Listeria monocytogenes-infected macrophages.
Project description:As a pathogenic microorganism, Listeria monocytogenes is widely used in the study of bacterial pathogenic mechanism and host defense mechanism. The lysosomal escape of Listeria monocytogenes is essential for its replication in the cytoplasm. Here, we report that Listeria monocytogenes infection can cause the expression level of Six-transmembrane epithelial antigen of the prostate 3 (Steap3) to decrease in macrophages. Functional experiments show that Steap3 can inhibit lysosomal escape of Listeria monocytogenes. Then, the comprehensive proteomic analysis reveals that the deletion of Steap3 affects the lysosomal signaling pathway of macrophages. Among these proteins affected by Steap3, we discover that Ganglioside GM2 activator (Gm2a) may be a potential target gene of Steap3. In summary, we find that Steap3-Gm2a axis can inhibits lysosomal escape of Listeria monocytogenes and serve the potential molecular drug targets for antibacterial treatment.
Project description:Transcriptional profling of a Listeria monocytogenes under nisin treatment comparing ctsR mutant and wild type one condition (nisin treament 20ug/ml, 24 hours) experiment, ctsR mutant vs. wild type Listeria monocytogenes Scott A, 2 biological replicates, 4 technical replicates
Project description:Listeria monocytogenes is a common clinical pathogen primarily transmitted among humans and animals through contaminated food. Currently, the increasing prevalence of antibiotic resistance due to the misuse of antibiotics has become a significant problem, leaving both clinical medicine and agriculture with a lack of effective treatments for Listeria infections. Listeriolysin O (LLO), a virulence factor secreted by Listeria monocytogenes, is a key factor in its pathogenicity. Strains of Listeria monocytogenes lacking the LLO gene are non-pathogenic to humans and animals. Therefore, studying the molecular mechanisms of LLO degradation is of great practical significance for treating clinical infections caused by antibiotic-resistant Listeria. Additionally, it will provide a theoretical basis for developing new antimicrobial drugs. Since Listeria monocytogenes secretes LLO throughout its entire life cycle within the host cell, understanding the fate of LLO at different stages of infection is crucial for elucidating the pathogenic mechanisms of Listeria monocytogenes. It is already known that LLO secreted by Listeria within the phagosome can be degraded via the lysosomal pathway. However, the fate of LLO secreted by Listeria in the cytoplasm remains poorly understood. Based on our previous experimental data and relevant literature, we propose a novel hypothesis that the AP-2 complex targets and degrades LLO secreted by Listeria in the cytoplasm.
