Recruitment and training of alveolar macrophages after pneumococcal pneumonia
Emad I. Arafa, Anukul T. Shenoy, Kimberly A. Barker, Neelou S. Etesami, Ian M.C. Martin, Carolina Lyon De Ana, Elim Na, Christine V. Odom, Wesley N. Goltry, Filiz T. Korkmaz, Alicia K. Wooten, Anna C. Belkina, Antoine Guillon, E. Camilla Forsberg, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd
Emad I. Arafa, Anukul T. Shenoy, Kimberly A. Barker, Neelou S. Etesami, Ian M.C. Martin, Carolina Lyon De Ana, Elim Na, Christine V. Odom, Wesley N. Goltry, Filiz T. Korkmaz, Alicia K. Wooten, Anna C. Belkina, Antoine Guillon, E. Camilla Forsberg, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd
View: Text | PDF
Research Article Immunology Pulmonology

Recruitment and training of alveolar macrophages after pneumococcal pneumonia

Abstract

Recovery from pneumococcal pneumonia remodels the pool of alveolar macrophages so that they exhibit new surface marker profiles, transcriptomes, metabolomes, and responses to infection. Mechanisms mediating alveolar macrophage phenotypes after pneumococcal pneumonia have not been delineated. IFN-γ and its receptor on alveolar macrophages were essential for certain, but not all, aspects of the remodeled alveolar macrophage phenotype. IFN-γ was produced by CD4+ T cells plus other cells, and CD4+ cell depletion did not prevent alveolar macrophage remodeling. In mice infected or recovering from pneumococcus, monocytes were recruited to the lungs, and the monocyte-derived macrophages developed characteristics of alveolar macrophages. CCR2 mediated the early monocyte recruitment but was not essential to the development of the remodeled alveolar macrophage phenotype. Lineage tracing demonstrated that recovery from pneumococcal pneumonias converted the pool of alveolar macrophages from being primarily of embryonic origin to being primarily of adult hematopoietic stem cell origin. Alveolar macrophages of either origin demonstrated similar remodeled phenotypes, suggesting that ontogeny did not dictate phenotype. Our data reveal that the remodeled alveolar macrophage phenotype in lungs recovered from pneumococcal pneumonia results from a combination of new recruitment plus training of both the original cells and the new recruits.

Authors

Emad I. Arafa, Anukul T. Shenoy, Kimberly A. Barker, Neelou S. Etesami, Ian M.C. Martin, Carolina Lyon De Ana, Elim Na, Christine V. Odom, Wesley N. Goltry, Filiz T. Korkmaz, Alicia K. Wooten, Anna C. Belkina, Antoine Guillon, E. Camilla Forsberg, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd

×

Figure 10

Recent recruits differ functionally from the AM that were initially resident in the experienced lung.

Options: View larger image (or click on image) Download as PowerPoint
Recent recruits differ functionally from the AM that were initially resi...
A lineage-tracing mouse model allowed the differentiation of AM of embryonic origin (TdTomato+) from those that derived from adult hematopoietic stem cells (GFP+). (A–G) Naive and experienced mice had prior exposures to saline or pneumococcus Sp19F in their lungs, respectively, before being challenged with a mismatched Sp3 serotype prior to AM collection for studies of cytokine expression (A–C) or phagocytosis (D–G). (A–C) Fold induction of Cxcl9 (A), Cxcl2 (B), and Il6 (C) transcripts measured using quantitative PCR of sorted tdTomato+ and GFP+ AM, normalized to average induction in naive tdTomato+ AM for each gene. n = 4–12 mice per group. Values are expressed as mean ± SEM, and unpaired Mann-Whitney U tests were used to examine the effect of experience on each AM subset. (D) Fraction of AM of distinct origin that were actively phagocytic within experienced lungs, expressed as the percentage of total AM of that origin (TdTomato+ or GFP+) that were associated with ClaretVue-labeled bacteria 40 minutes after instillation. (E) Amount of Sp3 phagocytized by AM that were actively phagocytic within experienced lungs, expressed as the MFI of those AM that were ClaretVue+. (D and E) n = 6 mice per group, with lines connecting AM subsets of distinct origin within a given mouse lung. (F) Fraction of AM of distinct origin that were actively phagocytic within naive lungs, expressed as the percentage of total AM of that origin (TdTomoato+ or GFP+) that were associated with ClaretVue-labeled bacteria 40 minutes after instillation. (G) Amount of Sp3 phagocytized by AM that were actively phagocytic within naive lungs, expressed as the MFI of those AM that were ClaretVue+. (F and G) n = 7 mice per group, with lines connecting AM subsets of distinct origin within a given mouse lung. The experienced mice in D and E and naive mice in F and G were collected in different experiments; therefore, data should not be compared across the former and latter panels. For D–G, paired t tests were used to examine significance.