Abstract
The incidence of mixed viral/bacterial infections has increased recently because of the dramatic increase in antibiotic-resistant strains, the emergence of new pathogens, and the resurgence of old ones. Despite the relatively well-known role of viruses in enhancing bacterial infections, the impact of bacterial infections on viral infections remains unknown. In this study, we provide direct evidence that nontypeable Haemophilus influenzae (NTHi), a major respiratory bacterial pathogen, augments the host antiviral response by up-regulating epithelial Toll-like receptor 7 (TLR7) expression in vitro and in vivo. Moreover, NTHi induces TLR7 expression via a TLR2-MyD88-IRAK-TRAF6-IKK-NF-kappaB-dependent signaling pathway. Interestingly, CYLD, a novel deubiquitinase, acts as a negative regulator of TLR7 induction by NTHi. Our study thus provides new insights into a novel role for bacterial infection in enhancing host antiviral response and further identifies CYLD for the first time as a critical negative regulator of host antiviral response.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cell Line
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Cysteine Endopeptidases / deficiency
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism*
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Cytokines / biosynthesis
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Deubiquitinating Enzyme CYLD
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Down-Regulation*
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Haemophilus influenzae / classification
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Haemophilus influenzae / physiology*
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Humans
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Lung Diseases / genetics
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Lung Diseases / metabolism
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Lung Diseases / microbiology
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Lung Diseases / virology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice
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Signal Transduction
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Toll-Like Receptor 2 / deficiency
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 2 / metabolism
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Toll-Like Receptor 7 / genetics
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Toll-Like Receptor 7 / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Up-Regulation*
Substances
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Cytokines
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Membrane Glycoproteins
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TLR2 protein, human
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TLR7 protein, human
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Tlr2 protein, mouse
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Tlr7 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 7
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Tumor Suppressor Proteins
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CYLD protein, human
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CYLD protein, mouse
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Deubiquitinating Enzyme CYLD
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Cysteine Endopeptidases