PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils
Autoři:
Lei Yue aff001; Min Yan aff002; Michel L. Tremblay aff003; Tong-Jun Lin aff004; Hua Li aff001; Ting Yang aff001; Xia Song aff001; Tianhong Xie aff001; Zhongping Xie aff001
Působiště autorů:
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China
aff001; Department of Microbiology and Immunology, Kunming Medical University, Kunming, Yunnan, China
aff002; Rosalind and Morris Goodman Cancer Research Centre, Department of Biochemistry, McGill University, Montréal, Quebec, Canada
aff003; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
aff004; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
aff005
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0222753
Souhrn
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-β, 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.
Klíčová slova:
Biology and life sciences – Cell biology – Biochemistry – Organisms – Research and analysis methods – Cell processes – Molecular biology – Neuroscience – Molecular biology techniques – Developmental biology – Cellular types – Animal cells – Medicine and health sciences – Microbiology – Medical microbiology – Microbial pathogens – Bacterial pathogens – Pseudomonas aeruginosa – Bacteria – Pseudomonas – Pathology and laboratory medicine – Pathogens – Physiology – Immunology – Immune system – Innate immune system – Cytokines – Immune physiology – Molecular development – Blood cells – White blood cells – Immune cells – Artificial gene amplification and extension – Polymerase chain reaction – Neurochemistry – Neurochemicals – Signal transduction – Cell signaling – Nitric oxide – Neutrophils – Phagocytosis – Membrane receptor signaling – Immune receptor signaling – STAT signaling
Zdroje
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