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Macrophage innate immune responses delineate between defective translocon assemblies produced by Yersinia pseudotuberculosis YopD mutants
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). (Francis)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). (Francis)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). (Francis)
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). (Wai)ORCID iD: 0000-0003-4793-4671
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2023 (English)In: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 14, no 1, article id 2249790Article in journal (Refereed) Published
Abstract [en]

Translocon pores formed in the eukaryotic cell membrane by a type III secretion system facilitate the translocation of immune-modulatory effector proteins into the host cell interior. The YopB and YopD proteins produced and secreted by pathogenic Yersinia spp. harboring a virulence plasmid-encoded type III secretion system perform this pore-forming translocator function. We had previously characterized in vitro T3SS function and in vivo pathogenicity of a number of strains encoding sited-directed point mutations in yopD. This resulted in the classification of mutants into three different classes based upon the severity of the phenotypic defects. To investigate the molecular and functional basis for these defects, we explored the effectiveness of RAW 264.7 cell line to respond to infection by representative YopD mutants of all three classes. Signature cytokine profiles could separate the different YopD mutants into distinct categories. The activation and suppression of certain cytokines that function as central innate immune response modulators correlated well with the ability of mutant bacteria to alter anti-phagocytosis and programmed cell death pathways. These analyses demonstrated that sub-optimal translocon pores impact the extent and magnitude of host cell responsiveness, and this limits the capacity of pathogenic Yersinia spp. to fortify against attack by both early and late arms of the host innate immune response.

Place, publisher, year, edition, pages
London: Taylor & Francis Group, 2023. Vol. 14, no 1, article id 2249790
Keywords [en]
Cytokine profiling, inflammasome, programmed cell death, anti-phagocytosis, translocon complexes, bacteria-eukaryotic cell contact
National Category
Microbiology in the medical area Microbiology
Research subject
Microbiology; Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-213952DOI: 10.1080/21505594.2023.2249790PubMedID: 37621095Scopus ID: 2-s2.0-85168743016OAI: oai:DiVA.org:umu-213952DiVA, id: diva2:1793420
Funder
Swedish Research Council, 2014-2105Umeå UniversitySwedish Research Council, 2018-02676Swedish Research Council, 2022-04779Swedish Research Council, 2018-02914The Kempe FoundationsAvailable from: 2023-08-31 Created: 2023-08-31 Last updated: 2023-09-07Bibliographically approved

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Farag, SalahFrancis, Monika K.Gurung, Jyoti M.Wai, Sun NyuntStenlund, HansFrancis, Matthew SNadeem, Aftab

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Farag, SalahFrancis, Monika K.Gurung, Jyoti M.Wai, Sun NyuntStenlund, HansFrancis, Matthew SNadeem, Aftab
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Department of Molecular Biology (Faculty of Medicine)Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Science and Technology)Molecular Infection Medicine Sweden (MIMS)Department of Plant Physiology
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Virulence
Microbiology in the medical areaMicrobiology

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