PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils.
PLoS One
; 14(9): e0222753, 2019.
Article
em En
| MEDLINE
| ID: mdl-31532798
ABSTRACT
Neutrophils play a critical role in host defense against Pseudomonas aeruginosa infection. Mechanisms underlying the negative regulation of neutrophil function in bacterial clearance remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of P. aeruginosa clearance by neutrophils. PTP1B-deficient neutrophils display greatly enhanced bacterial phagocytosis and killing, which are accompanied by increased Toll-like receptor 4 (TLR4) signaling activation and nitric oxide (NO) production following P. aeruginosa infection. Interestingly, PTP1B deficiency mainly upregulates the production of IL-6 and IFN-ß, leads to enhanced TLR4-dependent STAT1 activation and iNOS expression by neutrophils following P. aeruginosa infection. Further studies reveal that PTP1B and STAT1 are physically associated. These findings demonstrate a negative regulatory mechanism in neutrophil underlying the elimination of P. aeruginosa infection though a PTP1B-STAT1 interaction.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Infecções por Pseudomonas
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Proteína Tirosina Fosfatase não Receptora Tipo 1
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Neutrófilos
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Óxido Nítrico
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article