Identification of novel proteins associated with xenophagy in host cell
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Takashi Nozawa, Atsuko Minowa-Nozawa
PROVIDER: PXD038868 | JPOST Repository | Wed Dec 21 00:00:00 GMT 2022
REPOSITORIES: jPOST
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Project description:Almost all intracellular bacteria invade host cells through endocytic membrane trafficking. Bacteria that invade through endocytosis are rapidly transported to degradative organelles, therefore bacterial pathogens have evolved strategies to modulate intracellular bactericidal pathways during infection for survival and proliferation. On the other hand, the host cell also has a defensive system (xenophagy, a type of selective autophagy) against pathogens escaping from endosomes.
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Project description:Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate IFN-stimulated genes (ISGs). IFN-λ expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1+/- mice or when lntA was constitutively expressed. Thus the LntA-BAHD1 interplay may modulate IFN-λ−mediated immune response to control bacterial colonization of the host. In this dataset, we include the expression data obtained following infection of human Lovo cells infected with Listeria bacteria expressing (LntA-V5+) or not (DlntA) the virulence facteur LntA
2011-02-03 | GSE26414 | GEO
Project description:Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate IFN-stimulated genes (ISGs). IFN-M-NM-; expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1+/- mice or when lntA was constitutively expressed. Thus the LntA-BAHD1 interplay may modulate IFN-M-NM-;M-bM-^HM-^Rmediated immune response to control bacterial colonization of the host. In this dataset, we include the expression data obtained following infection of human Lovo cells infected with Listeria bacteria expressing (LntA-V5+) or not (DlntA) the virulence facteur LntA RNA from LoVo cells grown in 6-well plates and infected with either lntAV5+ or lntAM-bM-^@M-^S strains was extracted. Three biological replicates were analyzed for each experimental condition.
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Project description:We show that antigen internalization depends both on constitutive, clathrin-mediated endocytosis and on antigen-induced, clathrin-independent endocytosis mediated by endophilin A2. Although endophilin A2-mediated endocytosis is dispensable for antigen presentation, it is selectively required for metabolic support of B cell proliferation, in part through regulation of iron uptake. Consequently, endophilin A2 deficient mice show defects in GC B cell responses and production of high-affinity IgG. The requirement for endophilin A2 highlights a unique importance of clathrin-independent intracellular trafficking in GC B cell clonal expansion and antibody responses
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Project description:Background: It has been shown that intracellular pathogens hijack DC functions to evade immune defense mechanisms. In this study, we investigated the responses of human monocyte derived DCs to four intracellular bacteria, Tropheryma whipplei, Coxiella burnetii, Brucella abortus and Orientia tsutsugamushi, responsible for human infectious diseases and known to infect myeloid cells. Methods: Whole genome microarrays were assessed to define common and specific transcriptionnal responses to bacterial pathogen. Bacterial pathogen ability to affect DC maturation was assessed by measuring lymphoproliferation and endocytosis as well as phenotypic maturation markers (CD80, CD83, CD86 and HLA-DR) expression. Results: We found that Coxiella burnetii, Orientia tsutsugamushi and Brucella abortus induced DC maturation assessed through decreased endocytosis ability, triggering lymphoproliferation, surface expression of HLA class II molecules and phenotypic changes, whereas Tropheryma whipplei did not induce DC maturation. As revealed by microarray analysis, the response of DCs to these bacteria consisted of a core associated with the maturation of DCs and signatures specific for each pathogen. The core response represented 10% of genes modulated in response to pathogens and consisted of general cellular processes including nucleotide binding, protein transport, cell fraction, protein kinase, cell cycle, mitochondrial membrane and cytoskeleton. The specific transcriptional signature induced by C. burnetii is associated with the communication between innate and adaptive immune cells and DC maturation. B. abortus signature specifically involved arachidonic acid and lipooxygenase pathways and O. tsutsugamushi signature involved type I and type III IFN responses. Conclusion: This study demonstrates that intracellular bacteria use multifaceted pathways to induce DC maturation which may lead to unadapted immune response. The understanding of these pathways may be useful to improve our knowledge of bacterial recognition by the immune system but also intracellular bacterial diseases.
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