PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils

Lei Yue; Min Yan; Michel L. Tremblay; Tong Jun Lin; Hua Li; Ting Yang; Xia Song; Tianhong Xie; Zhongping Xie

doi:10.1371/journal.pone.0222753

PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils

Lei Yue, Min Yan, Michel L. Tremblay, Tong Jun Lin, Hua Li, Ting Yang, Xia Song, Tianhong Xie, Zhongping Xie

Medicine

Résultat de recherche: Article › examen par les pairs

7 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Numéro d'article	e0222753
Journal	PLoS One
Volume	14
Numéro de publication	9
DOI	https://doi.org/10.1371/journal.pone.0222753
Statut de publication	Published - sept. 1 2019

Note bibliographique

Funding Information:
This work received grant support from National Natural Science Foundation of China (81800012) (http://www.nsfc.gov.cn), Yunnan Natural Science Foundation (2016FB037, 2017FB019) (http://kjt.yn.gov.cn/), PUMC Youth Fund (3332016114) (http://www.cams.ac.cn) and Fundamental Research Funds for the Central Universities (2016ZX350070) (http://www.cams. ac.cn) to LY. MY has received grant support from National Natural Science Foundation of China (31560271) (http://www.nsfc.gov.cn). TJL has received grant support from National Natural Science Foundation of China (81471564) (http:// www.nsfc.gov.cn). ZX is supported by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-019) (http://www.cams.ac.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Ms. Chuhan Feng (McGill University, Montréal, Canada) and Dr. Zhaojun Wang (Shanghai Jiao Tong University School of Medicine, Shanghai, China) for input during the writing of the manuscript.

Publisher Copyright:
© 2019 Yue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus Subject Areas

General

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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title = "PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils",

abstract = "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.",

author = "Lei Yue and Min Yan and Tremblay, {Michel L.} and Lin, {Tong Jun} and Hua Li and Ting Yang and Xia Song and Tianhong Xie and Zhongping Xie",

note = "Funding Information: This work received grant support from National Natural Science Foundation of China (81800012) (http://www.nsfc.gov.cn), Yunnan Natural Science Foundation (2016FB037, 2017FB019) (http://kjt.yn.gov.cn/), PUMC Youth Fund (3332016114) (http://www.cams.ac.cn) and Fundamental Research Funds for the Central Universities (2016ZX350070) (http://www.cams. ac.cn) to LY. MY has received grant support from National Natural Science Foundation of China (31560271) (http://www.nsfc.gov.cn). TJL has received grant support from National Natural Science Foundation of China (81471564) (http:// www.nsfc.gov.cn). ZX is supported by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-019) (http://www.cams.ac.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Ms. Chuhan Feng (McGill University, Montr{\'e}al, Canada) and Dr. Zhaojun Wang (Shanghai Jiao Tong University School of Medicine, Shanghai, China) for input during the writing of the manuscript. Publisher Copyright: {\textcopyright} 2019 Yue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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AU - Song, Xia

AU - Xie, Tianhong

AU - Xie, Zhongping

N1 - Funding Information: This work received grant support from National Natural Science Foundation of China (81800012) (http://www.nsfc.gov.cn), Yunnan Natural Science Foundation (2016FB037, 2017FB019) (http://kjt.yn.gov.cn/), PUMC Youth Fund (3332016114) (http://www.cams.ac.cn) and Fundamental Research Funds for the Central Universities (2016ZX350070) (http://www.cams. ac.cn) to LY. MY has received grant support from National Natural Science Foundation of China (31560271) (http://www.nsfc.gov.cn). TJL has received grant support from National Natural Science Foundation of China (81471564) (http:// www.nsfc.gov.cn). ZX is supported by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-019) (http://www.cams.ac.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Ms. Chuhan Feng (McGill University, Montréal, Canada) and Dr. Zhaojun Wang (Shanghai Jiao Tong University School of Medicine, Shanghai, China) for input during the writing of the manuscript. Publisher Copyright: © 2019 Yue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

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PTP1B negatively regulates nitric oxide-mediated Pseudomonas aeruginosa killing by neutrophils

Résumé

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ASJC Scopus Subject Areas

PubMed: MeSH publication types

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