Macrophage Turnover Kinetics in the Lungs of Mice Infected with Streptococcus pneumoniae
Katharina Taut1, Christine Winter, David E Briles
1Department of Pulmonary Medicine, Laboratory for Experimental Lung Research, Hannover School of Medicine, Hannover, Germany.
Abstract:
Streptococcus pneumoniae is the most prevalent cause of community-acquired pneumonia and is known to induce apoptosis and necrosis in macrophages in vivo. We analyzed the kinetics of alveolar and lung parenchymal macrophage replacement by newly recruited exudate macrophages in vehicle-treated and S. pneumoniae-challenged bone marrow chimeric CD45.1 mice. After lethal irradiation, CD45.1 alloantigen-expressing recipient mice were transplanted with bone marrow cells from CD45.2 alloantigen-expressing donor mice. After only 24 hours of low-dose S. pneumoniae infection, approximately 60% of CD45.1(pos) recipient-type alveolar macrophages (AM) were replaced by CD45.2(pos) donor-type exudate AM in bronchoalveolar lavage fluid, and this increased to more than 80% on Day 7 of infection. In contrast, lung parenchymal macrophages of S. pneumoniae-infected chimeric CD45.1 mice were replaced by only about 10% by 24 hours, although this increased to over 80% by Days 3 to 7 of infection. This dramatic macrophage turnover was accompanied by early induction of apoptosis/necrosis in donor-type exudate AM peaking at 6 hours after infection, whereas peak apoptosis/necrosis induction in recipient-type AM was delayed until Day 7. Collectively, these data for the first time demonstrate that S. pneumoniae infection of the lung triggers a brisk turnover of both resident and recruited mononuclear phagocyte subsets, and suggest an important role of exudate but not resident macrophages in re-establishing alveolar and lung homeostasis.
Insights
Streptococcus pneumoniae infection rapidly replaces lung macrophages. Exudate macrophages are crucial for restoring alveolar and lung homeostasis after pneumonia.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Streptococcus pneumoniae is a leading cause of community-acquired pneumonia.
- Pneumonia induced by S. pneumoniae causes macrophage apoptosis and necrosis.
- Understanding macrophage dynamics during infection is vital for therapeutic strategies.
Purpose of the Study:
- To investigate the kinetics of alveolar and lung parenchymal macrophage replacement during S. pneumoniae infection.
- To differentiate the roles of resident and recruited macrophages in lung homeostasis post-infection.
Main Methods:
- Utilized bone marrow chimeric mice (CD45.1 and CD45.2) to track macrophage populations.
- Administered low-dose S. pneumoniae infection to chimeric mice.
- Analyzed macrophage replacement and apoptosis/necrosis in alveolar and lung parenchymal macrophages over time.
Main Results:
- S. pneumoniae infection led to rapid replacement of alveolar macrophages (AM) by exudate AM within 24 hours (60%) and by Day 7 (over 80%).
- Lung parenchymal macrophages showed slower replacement, with 10% turnover at 24 hours increasing to over 80% by Days 3-7.
- Exudate macrophages exhibited early apoptosis/necrosis peaking at 6 hours, while resident macrophages showed delayed peak apoptosis/necrosis at Day 7.
Conclusions:
- S. pneumoniae infection triggers significant and rapid turnover of both resident and recruited mononuclear phagocyte subsets in the lung.
- Exudate macrophages play a critical role in re-establishing alveolar and lung homeostasis following S. pneumoniae infection.
- Resident macrophages appear less critical in the immediate post-infection recovery phase.
