Abstract
Interferons (IFNs) induce an anti-microbial state, protecting tissues from infection. Many viruses antagonize IFN signaling, but whether bacterial pathogens also evade IFN responses remains unclear. Here, we demonstrate that the Shigella OspC family of type III-secreted effectors blocks signaling from all IFNs. The growth of Shigella lacking OspC1 and OspC3 was attenuated in epithelial cells in the presence of IFN, and in a murine model of infection. IFN inhibition was mediated by binding of OspC1 and OspC3 to the Ca2+ sensor calmodulin (CaM), blocking CaM kinase II and downstream JAK/STAT signaling. OspC effector proteins were conserved in other human pathogens. OspC homologs not only bound CaM but also inhibited IFN, suggesting that these bacteria share a common virulence strategy. These findings reveal a conserved but previously undescribed molecular mechanism of IFN inhibition, and demonstrate the critical role of Ca2+ and IFN targeting by pathogenic bacteria.
Original language | English |
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Pages (from-to) | 2354-2369.e17 |
Journal | Cell |
Volume | 185 |
Issue number | 13 |
Early online date | 23 Jun 2022 |
DOIs | |
Publication status | Published - 23 Jun 2022 |