Related Experiment Video
Updated: Jul 2, 2026
Flow Cytometric Analysis for Identification of the Innate and Adaptive Immune Cells of Murine Lung
Published on: November 16, 2021
Dynamics of lung macrophage activation in response to helminth infection
Mark C Siracusa1, Joshua J Reece, Joseph F Urban
1The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Abstract:
Most of our understanding of the development and phenotype of alternatively activated macrophages (AAMs) has been obtained from studies investigating the response of bone marrow- and peritoneal-derived cells to IL-4 or IL-13 stimulation. Comparatively little is known about the development of AAMs in the lungs, and how the complex signals associated with pulmonary inflammation influence the AAM phenotype. Here, we use Nippostrongylus brasiliensis to initiate AAM development and define the dynamics of surface molecules, gene expression, and cell function of macrophages isolated from lung tissue at different times postinfection (PI). Initially, lung macrophages take on a foamy phenotype, up-regulate MHC and costimulatory molecules, express reduced levels of TNF and IL-12, and undergo proliferation. Cells isolated between days 8 and 15 PI adopt a dense, granular phenotype and exhibit reduced levels of costimulatory molecules and elevated levels of programmed death ligand-1 (PDL-1) and PDL-2 and an increase in IL-10 expression. Functionally, AAMs isolated on days 13-15 PI demonstrate an enhanced capacity to take up and sequester antigen. However, these same cells did not mediate antigen-specific T cell proliferation and dampened the proliferation of CD3/CD28-activated CD4+ T cells. These data indicate that the alternative activation of macrophages in the lungs, although initiated by IL-4/IL-13, is a dynamic process that is likely to be influenced by other immune and nonimmune factors in the pulmonary environment.
Insights
Lung macrophages develop dynamically during infection, changing phenotype and function. These alternatively activated macrophages (AAMs) can suppress T cell responses, indicating complex regulation beyond IL-4/IL-13.
Area of Science:
- Immunology
- Macrophage Biology
- Pulmonary Inflammation
Background:
- Understanding of alternatively activated macrophages (AAMs) primarily comes from bone marrow and peritoneal cells stimulated with IL-4/IL-13.
- Limited knowledge exists regarding lung AAM development and the influence of pulmonary inflammation on their phenotype.
Purpose of the Study:
- To investigate the dynamic development and phenotype of lung macrophages during helminth infection.
- To characterize changes in surface molecules, gene expression, and cell function of lung macrophages postinfection.
Main Methods:
- Utilized Nippostrongylus brasiliensis infection model in mice.
- Isolated lung macrophages at various time points postinfection (PI).
- Analyzed surface molecule expression, gene expression, and cellular functions, including antigen uptake and T cell proliferation assays.
Main Results:
- Early lung macrophages exhibited a foamy phenotype, up-regulated MHC and costimulatory molecules, and reduced TNF/IL-12. They also proliferated.
- Later, macrophages (days 8-15 PI) showed a dense, granular phenotype with decreased costimulatory molecules, increased PDL-1/PDL-2, and elevated IL-10.
- Macrophages from days 13-15 PI enhanced antigen uptake but suppressed antigen-specific T cell proliferation.
Conclusions:
- Alternative macrophage activation in the lungs is a dynamic process influenced by factors beyond IL-4/IL-13.
- Lung AAMs exhibit distinct functional characteristics, including antigen sequestration and T cell suppression.
- Pulmonary environment significantly shapes AAM phenotype and function during infection.
More Related Videos
10:39Advanced Imaging of Lung Homing Human Lymphocytes in an Experimental In Vivo Model of Allergic Inflammation Based on Light-sheet Microscopy
Published on: April 16, 2019
08:34Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
