Pneumonia recovery reprograms the alveolar macrophage pool
Antoine Guillon, … , Lee J. Quinton, Joseph P. Mizgerd
Antoine Guillon, … , Lee J. Quinton, Joseph P. Mizgerd
Published January 28, 2020
Citation Information: JCI Insight. 2020;5(4):e133042. https://doi.org/10.1172/jci.insight.133042.
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Research Article Pulmonology

Pneumonia recovery reprograms the alveolar macrophage pool

Abstract

Community-acquired pneumonia is a widespread disease with significant morbidity and mortality. Alveolar macrophages are tissue-resident lung cells that play a crucial role in innate immunity against bacteria that cause pneumonia. We hypothesized that alveolar macrophages display adaptive characteristics after resolution of bacterial pneumonia. We studied mice 1 to 6 months after self-limiting lung infections with Streptococcus pneumoniae, the most common cause of bacterial pneumonia. Alveolar macrophages, but not other myeloid cells, recovered from the lung showed long-term modifications of their surface marker phenotype. The remodeling of alveolar macrophages was (a) long-lasting (still observed 6 months after infection), (b) regionally localized (observed only in the affected lobe after lobar pneumonia), and (c) associated with macrophage-dependent enhanced protection against another pneumococcal serotype. Metabolomic and transcriptomic profiling revealed that alveolar macrophages of mice that recovered from pneumonia had new baseline activities and altered responses to infection that better resembled those of adult humans. The enhanced lung protection after mild and self-limiting bacterial respiratory infections includes a profound remodeling of the alveolar macrophage pool that is long-lasting; compartmentalized; and manifest across surface receptors, metabolites, and both resting and stimulated transcriptomes.

Authors

Antoine Guillon, Emad I. Arafa, Kimberly A. Barker, Anna C. Belkina, Ian Martin, Anukul T. Shenoy, Alicia K. Wooten, Carolina Lyon De Ana, Anqi Dai, Adam Labadorf, Jaileene Hernandez Escalante, Hans Dooms, Hélène Blasco, Katrina E. Traber, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd

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Figure 2

Immunophenotyping of lung myeloid cells 1 month after recovery from mild pneumonia.

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Immunophenotyping of lung myeloid cells 1 month after recovery from mild...
(A) Defense against a serotype 3 pneumococcal pneumonia in naive mice and experienced (Exp’d) mice with a history of serotype 19F pneumococcal infections as described in Figure 1. Naive or experienced mice were infected intranasally (i.n.) with 0.5 × 106 to 1 × 106 CFU, and lung bacterial burdens were determined after 24 hours of infection. Asterisk (*) indicates statistically significant (P < 0.05) difference between groups using Mann-Whitney U test. For B and C, mice received intratracheally (i.t.) left lobe serotype 19F infections (Exp’d) or saline instillations (Naive) on days 0 and 7, before left lung lobes were collected at day 37 with no further infections. (B) Gating strategy for myeloid cells in lung single-cell suspensions. Cells were isolated from enzymatically digested mouse lungs, and after the exclusion of doublets, debris, and dead cells, immune cells were identified by CD45 staining. Sequential gating strategy was used to identify myeloid cell subsets. Representative sample from the naive group is shown. (C) Absolute cell counts of identified myeloid cell subsets were obtained and compared. Numbers per mouse were plotted for each cell type, with data collected over 2 independent experiments and each data point representing an individual animal. Groups were compared using 2-tailed Student’s t test, and naive and experienced mice did not significantly differ for any cell type. AM, alveolar macrophages; cDC, conventional dendritic cells; eos, eosinophils; IM, interstitial macrophages; monos, monocytes; neutro, neutrophils; pDC, plasmacytoid dendritic cells.