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Neutrophil Heterogeneity Is Modified during Acute Lung Inflammation in Apoa1-/- Mice
Xianglan Yao1, Neelam R Redekar2, Karen J Keeran3
1Laboratory of Asthma and Lung Inflammation, Critical Care Medicine and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Journal of Immunology (Baltimore, Md. : 1950)
|June 24, 2024
Summary
Apolipoprotein A-I influences immune cell populations in airway inflammation. Studies show its absence increases specific neutrophil and macrophage clusters, contributing to inflammation.
Area of Science:
- Immunology
- Respiratory Medicine
- Molecular Biology
Background:
- Neutrophils are key players in inflammatory airway diseases.
- Apolipoprotein A-I (Apoa1) is known to have anti-inflammatory properties.
- The precise mechanisms by which Apoa1 modulates immune responses in the airways are not fully understood.
Purpose of the Study:
- To investigate whether apolipoprotein A-I (Apoa1) modifies neutrophil heterogeneity.
- To determine if Apoa1's effect on neutrophil heterogeneity contributes to its anti-inflammatory mechanism in acute airway inflammation.
Main Methods:
- Acute neutrophilic airway inflammation was induced in apolipoprotein A-I deficient (Apoa1-/-) and wild-type (Apoa1+/+) mice using LPS plus house dust mite (LPS+HDM).
- Single-cell RNA sequencing was performed on bronchoalveolar lavage fluid cells.
- Unsupervised profiling and trajectory analysis were used to identify and characterize neutrophil and macrophage populations.
Main Results:
- Apoa1-/- mice exhibited increased proportions of specific neutrophil clusters (Neu4, Neu6) with distinct characteristics, including high maturation, aggregation, and pro-inflammatory gene expression (S100a8, S100a9, Mmp8).
- Neutrophil clusters expressing IFN-stimulated genes were decreased in Apoa1-/- mice.
- An increase in recruited airspace macrophages and a decrease in resident macrophages were observed in Apoa1-/- mice.
- All neutrophils and macrophages in LPS+HDM-challenged Apoa1-/- mice showed enhanced expression of pro-inflammatory genes (S100a8, S100a9, Lcn2).
Conclusions:
- Apoa1 deficiency leads to significant alterations in neutrophil and macrophage heterogeneity in the lung during acute LPS+HDM-induced inflammation.
- These changes in immune cell populations and their pro-inflammatory gene expression suggest a mechanism by which Apoa1 attenuates airway inflammation.
- Modifications in neutrophil and macrophage heterogeneity are critical components of Apoa1's anti-inflammatory effects in the airways.
