A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4

Charles V. Rosadini, Ivan Zanoni, Charlotte Odendall, Erin R. Green, Michelle K. Paczosa, Naomi H. Philip, Igor E. Brodsky, Joan Mecsas, Jonathan C. Kagan

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

During bacterial infections, Toll-like receptor 4 (TLR4) signals through the MyD88- and TRIF-dependent pathways to promote pro-inflammatory and interferon (IFN) responses, respectively. Bacteria can inhibit the MyD88 pathway, but if the TRIF pathway is also targeted is unclear. We demonstrate that, in addition to MyD88, Yersinia pseudotuberculosis inhibits TRIF signaling through the type III secretion system effector YopJ. Suppression of TRIF signaling occurs during dendritic cell (DC) and macrophage infection and prevents expression of type I IFN and pro-inflammatory cytokines. YopJ-mediated inhibition of TRIF prevents DCs from inducing natural killer (NK) cell production of antibacterial IFNγ. During infection of DCs, YopJ potently inhibits MAPK pathways but does not prevent activation of IKK- or TBK1-dependent pathways. This singular YopJ activity efficiently inhibits TLR4 transcription-inducing activities, thus illustrating a simple means by which pathogens impede innate immunity.
Original languageEnglish
Pages (from-to)682-93
JournalCell Host & Microbe
Volume18
Issue number6
Early online date9 Dec 2015
DOIs
Publication statusPublished - 9 Dec 2015

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