Protein Tyrosine Phosphatase-1B Negatively Impacts Host Defense against Pseudomonas aeruginosa Infection.
Pseudomonas aeruginosa is a major opportunistic pathogen in immune-compromised individuals. Mechanisms governing immune responses to P. aeruginosa infection remain incompletely defined. Herein, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator in P. aeruginosa infection. PTP1B-deficient mice display greatly enhanced bacterial clearance and reduced disease scores, which are accompanied by increased neutrophil infiltration and cytokine production. Interestingly, PTP1B deficiency mainly up-regulates the production of interferon-stimulated response elements-regulated cytokines and chemokines, including chemokine ligand 5 (regulated on activation normal T cell expressed and secreted), CXCL10 (interferon γ-inducible protein 10), and interferon-β production. Further studies reveal that PTP1B deficiency leads to increased interferon regulatory factor 7 (IRF7) expression and activation. These findings demonstrate a novel regulatory mechanism of the immune response to P. aeruginosa infection through PTP1B-IRF7 interaction. This novel PTP1B-IRF7-interferon-stimulated response elements pathway may have broader implications in Toll-like receptor-mediated innate immunity.
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
Lei
L
Yue
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
Zhongping
Z
Xie
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
Hua
H
Li
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Zheng
Z
Pang
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Robert D
RD
Junkins
Department of Biochemistry, Goodman Cancer Research Centre, McGill University, Montréal, Quebec, Canada.
Michel L
ML
Tremblay
Department of Neurology, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, China.
Xiaochun
X
Chen
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada; Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia, Canada. Electronic address: tong-jun.lin@dal.ca.
Tong-Jun
TJ
Lin
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D066298:In Vitro Techniques; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D008171:Lung Diseases / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000172:deficiency* / Q000276:immunology; D011552:Pseudomonas Infections / Q000201:enzymology* / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D000907:Antibodies, Bacterial; D018925:Chemokines; D016207:Cytokines; D050839:Interferon Regulatory Factor-7; D016328:NF-kappa B; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1