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Updated: May 5, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
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.
Insights
Lipocalin 2 (LCN2) deactivates macrophages, suppressing inflammation and impairing bacterial clearance. Elevated LCN2 in pneumonia indicates a worse outcome, highlighting its role in infection severity.
Area of Science:
- Immunology
- Microbiology
- Respiratory Medicine
Background:
- Macrophages are crucial for pathogen response and inflammation.
- Deactivated macrophages resolve inflammation but lack specific markers.
- Understanding macrophage subsets is key to infection outcomes.
Purpose of the Study:
- Identify markers for deactivated macrophages.
- Investigate the role of lipocalin 2 (LCN2) in macrophage deactivation.
- Determine LCN2's impact on bacterial pneumonia and survival.
Main Methods:
- Identified LCN2 as a marker and deactivator of macrophages.
- Assessed LCN2's effect on inflammatory response and bacterial clearance in mice.
- Analyzed LCN2 and IL-10 induction via STAT3 signaling.
- Correlated pulmonary LCN2 levels with human pneumonia outcomes.
Main Results:
- LCN2 attenuated early inflammation and impaired bacterial clearance in pneumococcal pneumonia models.
- LCN2 induced interleukin-10 (IL-10) production by macrophages, promoting a STAT3-dependent polarization.
- Human bacterial pneumonia showed elevated pulmonary LCN2 levels.
- High LCN2 levels correlated with detrimental outcomes in Gram-positive bacterial pneumonia.
Conclusions:
- Macrophage deactivation is critical for pneumococcal infection outcomes.
- LCN2 acts as a key deactivator of macrophages in the respiratory tract.
- LCN2 and IL-10 are significant determinants of macrophage function during respiratory infections.
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