Summary 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.

Rosadini, C., Zanoni, I., Odendall, C., Green, E., Paczosa, M., Philip, N., et al. (2015). A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4. CELL HOST & MICROBE, 18(6), 682-693 [10.1016/j.chom.2015.11.006].

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

ZANONI, IVAN
Secondo
;
2015

Abstract

Summary 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.
Articolo in rivista - Articolo scientifico
Adaptor Proteins, Vesicular Transport; Animals; Bacterial Proteins; Cells, Cultured; Dendritic Cells; Macrophages; Mice; Myeloid Differentiation Factor 88; Toll-Like Receptor 4; Yersinia pseudotuberculosis; Host-Pathogen Interactions; Immune Evasion; Signal Transduction; Immunology and Microbiology (all); Cancer Research; Molecular Biology
English
682
693
12
Rosadini, C., Zanoni, I., Odendall, C., Green, E., Paczosa, M., Philip, N., et al. (2015). A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4. CELL HOST & MICROBE, 18(6), 682-693 [10.1016/j.chom.2015.11.006].
Rosadini, C; Zanoni, I; Odendall, C; Green, E; Paczosa, M; Philip, N; Brodsky, I; Mecsas, J; Kagan, J
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/134601
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