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- W3204341217 abstract "Cellular ionic concentrations are a central factor orchestrating host innate immunity, but no pathogenic mechanism that perturbs host innate immunity by directly targeting metal ions has yet been described. Here, we report a unique virulence strategy of Yersinia pseudotuberculosis (Yptb) involving modulation of the availability of Mn2+, an immunostimulatory metal ion in host cells. We showed that the Yptb type VI secretion system (T6SS) delivered a micropeptide, TssS, into host cells to enhance its virulence. The mutant strain lacking TssS (ΔtssS) showed substantially reduced virulence but induced a significantly stronger host innate immune response, indicating an antagonistic role of this effector in host antimicrobial immunity. Subsequent studies revealed that TssS is a Mn2+-chelating protein and that its Mn2+-chelating ability is essential for the disruption of host innate immunity. Moreover, we showed that Mn2+ enhances the host innate immune response to Yptb infection by activating the stimulator of interferon genes (STING)-mediated immune response. Furthermore, we demonstrated that TssS counteracted the cytoplasmic Mn2+ increase to inhibit the STING-mediated innate immune response by sequestering Mn2+ Finally, TssS-mediated STING inhibition sabotaged bacterial clearance in vivo. These results reveal a previously unrecognized bacterial immune evasion strategy involving modulation of the bioavailability of intracellular metal ions and provide a perspective on the role of the T6SS in pathogenesis." @default.
- W3204341217 created "2021-10-11" @default.
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- W3204341217 date "2021-10-08" @default.
- W3204341217 modified "2023-09-23" @default.
- W3204341217 title "T6SS translocates a micropeptide to suppress STING-mediated innate immunity by sequestering manganese" @default.
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- W3204341217 doi "https://doi.org/10.1073/pnas.2103526118" @default.
- W3204341217 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8545469" @default.
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- W3204341217 hasPublicationYear "2021" @default.
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