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: 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 – Cellular types – Animal cells – Blood cells – White blood cells – Neutrophils – Immune cells – Cell processes – Phagocytosis – Signal transduction – Cell signaling – Membrane receptor signaling – Immune receptor signaling – STAT signaling – Microbiology – Medical microbiology – Microbial pathogens – Bacterial pathogens – Pseudomonas aeruginosa – Organisms – Bacteria – Pseudomonas – Biochemistry – Neurochemistry – Neurochemicals – Nitric oxide – Neuroscience – Molecular biology – Molecular biology techniques – Artificial gene amplification and extension – Polymerase chain reaction – Physiology – Developmental biology – Molecular development – Medicine and health sciences – Immunology – Immune system – Innate immune system – Cytokines – Pathology and laboratory medicine – Pathogens – Immune physiology – Research and analysis methods


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