First Author | Yue L | Year | 2019 |
Journal | PLoS One | Volume | 14 |
Issue | 9 | Pages | e0222753 |
PubMed ID | 31532798 | Mgi Jnum | J:279962 |
Mgi Id | MGI:6361401 | Doi | 10.1371/journal.pone.0222753 |
Citation | Yue L, et al. (2019) PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils. PLoS One 14(9):e0222753 |
abstractText | 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-beta, 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. |