Beneficial innate signaling interference for antibacterial responses by a Toll-like receptor–mediated enhancement of the MKP-IRF3 axis
Copyright policy )Beneficial innate signaling interference for antibacterial responses by a Toll-like receptor–mediated enhancement of the MKP-IRF3 axis
Significance Infection by a given pathogen results in stimulation of multiple classes of innate receptors in a cell, leading to activation of distinct signaling pathways. However, these pathways are not always beneficial to immune response against the pathogen. This study shows that, on infection by pathogenic bacterium Listeria monocytogenes , Toll-like receptor (TLR) pathways suppress type I IFN gene induction that is mediated by stimulator of IFN genes. Type I IFNs are critical for antiviral immunity but detrimental to macrophage bactericidal activity. The TLR pathways selectively suppress IFN regulatory factor 3, an essential transcription factor for type I IFN gene induction, through induction/activation of mitogen-activated protein kinase phosphatases, revealing a unique mechanism of beneficial innate signaling interference against bacterial infection.
- University of Tokyo Japan
- National University of Singapore Singapore
- Japan Science and Technology Agency Japan
- Yale University United States
- RIKEN Center for Integrative Medical Sciences (IMS), Yokohama City, Japan Japan
Mice, Knockout, Immunoblotting, Toll-Like Receptors, 610, Dual Specificity Phosphatase 1, Protein Serine-Threonine Kinases, Real-Time Polymerase Chain Reaction, 530, Listeria monocytogenes, Immunity, Innate, Colony-Forming Units Assay, Mice, Inbred C57BL, Mice, Multiprotein Complexes, Interferon Type I, Myeloid Differentiation Factor 88, Animals, Immunoprecipitation, Interferon Regulatory Factor-3, Listeriosis, Signal Transduction
Mice, Knockout, Immunoblotting, Toll-Like Receptors, 610, Dual Specificity Phosphatase 1, Protein Serine-Threonine Kinases, Real-Time Polymerase Chain Reaction, 530, Listeria monocytogenes, Immunity, Innate, Colony-Forming Units Assay, Mice, Inbred C57BL, Mice, Multiprotein Complexes, Interferon Type I, Myeloid Differentiation Factor 88, Animals, Immunoprecipitation, Interferon Regulatory Factor-3, Listeriosis, Signal Transduction
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