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Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes

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Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes. / Warszawska, Joanna M; Gawish, Riem; Sharif, Omar; Sigel, Stefanie; Doninger, Bianca; Lakovits, Karin; Mesteri, Ildiko; Nairz, Manfred; Boon, Louis; Spiel, Alexander; Fuhrmann, Valentin; Strobl, Birgit; Müller, Mathias; Schenk, Peter; Weiss, Günter; Knapp, Sylvia.

in: J CLIN INVEST, Jahrgang 123, Nr. 8, 01.08.2013, S. 3363-72.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Warszawska, JM, Gawish, R, Sharif, O, Sigel, S, Doninger, B, Lakovits, K, Mesteri, I, Nairz, M, Boon, L, Spiel, A, Fuhrmann, V, Strobl, B, Müller, M, Schenk, P, Weiss, G & Knapp, S 2013, 'Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes', J CLIN INVEST, Jg. 123, Nr. 8, S. 3363-72. https://doi.org/10.1172/JCI67911

APA

Warszawska, J. M., Gawish, R., Sharif, O., Sigel, S., Doninger, B., Lakovits, K., Mesteri, I., Nairz, M., Boon, L., Spiel, A., Fuhrmann, V., Strobl, B., Müller, M., Schenk, P., Weiss, G., & Knapp, S. (2013). Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes. J CLIN INVEST, 123(8), 3363-72. https://doi.org/10.1172/JCI67911

Vancouver

Warszawska JM, Gawish R, Sharif O, Sigel S, Doninger B, Lakovits K et al. Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes. J CLIN INVEST. 2013 Aug 1;123(8):3363-72. https://doi.org/10.1172/JCI67911

Bibtex

@article{bdfeafbc727243069413d62dbbe6aa3f,
title = "Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes",
abstract = "Macrophages play a key role in responding to pathogens and initiate an inflammatory response to combat microbe multiplication. Deactivation of macrophages facilitates resolution of the inflammatory response. Deactivated macrophages are characterized by an immunosuppressive phenotype, but the lack of unique markers that can reliably identify these cells explains the poorly defined biological role of this macrophage subset. We identified lipocalin 2 (LCN2) as both a marker of deactivated macrophages and a macrophage deactivator. We show that LCN2 attenuated the early inflammatory response and impaired bacterial clearance, leading to impaired survival of mice suffering from pneumococcal pneumonia. LCN2 induced IL-10 formation by macrophages, skewing macrophage polarization in a STAT3-dependent manner. Pulmonary LCN2 levels were tremendously elevated during bacterial pneumonia in humans, and high LCN2 levels were indicative of a detrimental outcome from pneumonia with Gram-positive bacteria. Our data emphasize the importance of macrophage deactivation for the outcome of pneumococcal infections and highlight the role of LCN2 and IL-10 as determinants of macrophage performance in the respiratory tract.",
keywords = "Acute-Phase Proteins, Adult, Aged, Animals, Female, Humans, Immune Tolerance, Interleukin-10, Lipocalins, Lung, Macrophage Activation, Macrophages, Alveolar, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Oncogene Proteins, Pneumonia, Pneumococcal, Proto-Oncogene Proteins, Transplantation Chimera",
author = "Warszawska, {Joanna M} and Riem Gawish and Omar Sharif and Stefanie Sigel and Bianca Doninger and Karin Lakovits and Ildiko Mesteri and Manfred Nairz and Louis Boon and Alexander Spiel and Valentin Fuhrmann and Birgit Strobl and Mathias M{\"u}ller and Peter Schenk and G{\"u}nter Weiss and Sylvia Knapp",
year = "2013",
month = aug,
day = "1",
doi = "10.1172/JCI67911",
language = "English",
volume = "123",
pages = "3363--72",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "8",

}

RIS

TY - JOUR

T1 - Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes

AU - Warszawska, Joanna M

AU - Gawish, Riem

AU - Sharif, Omar

AU - Sigel, Stefanie

AU - Doninger, Bianca

AU - Lakovits, Karin

AU - Mesteri, Ildiko

AU - Nairz, Manfred

AU - Boon, Louis

AU - Spiel, Alexander

AU - Fuhrmann, Valentin

AU - Strobl, Birgit

AU - Müller, Mathias

AU - Schenk, Peter

AU - Weiss, Günter

AU - Knapp, Sylvia

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Macrophages play a key role in responding to pathogens and initiate an inflammatory response to combat microbe multiplication. Deactivation of macrophages facilitates resolution of the inflammatory response. Deactivated macrophages are characterized by an immunosuppressive phenotype, but the lack of unique markers that can reliably identify these cells explains the poorly defined biological role of this macrophage subset. We identified lipocalin 2 (LCN2) as both a marker of deactivated macrophages and a macrophage deactivator. We show that LCN2 attenuated the early inflammatory response and impaired bacterial clearance, leading to impaired survival of mice suffering from pneumococcal pneumonia. LCN2 induced IL-10 formation by macrophages, skewing macrophage polarization in a STAT3-dependent manner. Pulmonary LCN2 levels were tremendously elevated during bacterial pneumonia in humans, and high LCN2 levels were indicative of a detrimental outcome from pneumonia with Gram-positive bacteria. Our data emphasize the importance of macrophage deactivation for the outcome of pneumococcal infections and highlight the role of LCN2 and IL-10 as determinants of macrophage performance in the respiratory tract.

AB - Macrophages play a key role in responding to pathogens and initiate an inflammatory response to combat microbe multiplication. Deactivation of macrophages facilitates resolution of the inflammatory response. Deactivated macrophages are characterized by an immunosuppressive phenotype, but the lack of unique markers that can reliably identify these cells explains the poorly defined biological role of this macrophage subset. We identified lipocalin 2 (LCN2) as both a marker of deactivated macrophages and a macrophage deactivator. We show that LCN2 attenuated the early inflammatory response and impaired bacterial clearance, leading to impaired survival of mice suffering from pneumococcal pneumonia. LCN2 induced IL-10 formation by macrophages, skewing macrophage polarization in a STAT3-dependent manner. Pulmonary LCN2 levels were tremendously elevated during bacterial pneumonia in humans, and high LCN2 levels were indicative of a detrimental outcome from pneumonia with Gram-positive bacteria. Our data emphasize the importance of macrophage deactivation for the outcome of pneumococcal infections and highlight the role of LCN2 and IL-10 as determinants of macrophage performance in the respiratory tract.

KW - Acute-Phase Proteins

KW - Adult

KW - Aged

KW - Animals

KW - Female

KW - Humans

KW - Immune Tolerance

KW - Interleukin-10

KW - Lipocalins

KW - Lung

KW - Macrophage Activation

KW - Macrophages, Alveolar

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Middle Aged

KW - Oncogene Proteins

KW - Pneumonia, Pneumococcal

KW - Proto-Oncogene Proteins

KW - Transplantation Chimera

U2 - 10.1172/JCI67911

DO - 10.1172/JCI67911

M3 - SCORING: Journal article

C2 - 23863624

VL - 123

SP - 3363

EP - 3372

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 8

ER -