PTP1B is a negative regulator in the host defense against Pseudomonas aeruginosa infection

International Conference and Exhibition on Lung Disorders & Therapeutics

July 13-15, 2015 Baltimore, Maryland, USA

Tong-Jun Lin1,2, Zhongping Xie1, Hua Li1, Robert D Junkins2, Michel L Tremblay3, Xiaochun Chen4 and Lei Yue1

Scientific Tracks Abstracts: J Pulm Respir Med

Abstract :

P seudomonas aeruginosa is a major opportunistic pathogen in immune-compromised individuals. Toll-like receptors (TLRs) contribute to innate immunity against P. aeruginosa through activation of transcription factors IRF7/IRF3 and NFκB. However, mechanisms involved in the regulation of P. aeruginosa-induced TLR pathway activation remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator in P. aeruginosa infection. PTP1Bdeficient mice display greatly enhanced bacterial clearance which is accompanied with increased neutrophil infiltration and cytokine production. Interestingly, PTP1B-deficiency mainly up-regulates the production of IFN-stimulated response elements (ISRE)- regulated cytokines and chemokines including CCL5 (RANTES), CXCL10 (IP-10) and IFN-β production. Further studies reveal that PTP1B-deficiency leads to increased IRF7 activation. Importantly, PTP1B is physically associated with IRF7 in dendritic cells. These findings demonstrate a novel regulatory mechanism of the immune response to P. aeruginosa infection through PTP1B-IRF7 interaction. This novel PTP1B-IRF7-ISRE pathway may have broader implications inTLR-mediated innate immunity.

Biography :

Tong-Jun Lin is working as a Professor in Department of Microbiology and Immunology. His research interests include signaling mechanisms in allergy, host defense mechanisms against bacterial infection, and immune response in cancer development. His work is interdisciplinary, collaborative and geared both to contributing to the academic literature and to developing immunological therapeutic approaches in inflammation.