Distinct Transcriptional and Functional Differences of Lung Resident and Monocyte-Derived Alveolar Macrophages During the Recovery Period of Acute Lung Injury
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In acute lung injury, two subsets of lung macrophages exist in the alveoli: tissue-resident alveolar macrophages (AMs) and monocyte-derived alveolar macrophages (MDMs). However, it is unclear whether these 2 subsets of macrophages have different functions and characteristics during the recovery phase. RNA-sequencing of AMs and MDMs from the recovery period of LPS-induced lung injury mice revealed their differences in proliferation, cell death, phagocytosis, inflammation and tissue repair. Using flow cytometry, we found that AMs showed a higher ability to proliferate, whereas MDMs expressed a larger amount of cell death. We also compared the ability of phagocytosing apoptotic cells and activating adaptive immunity and found that AMs have a stronger ability to phagocytose, while MDMs are the cells that activate lymphocytes during the resolving phase. By testing surface markers, we found that MDMs were more prone to the M1 phenotype, but expressed a higher level of pro-repairing genes. Finally, analysis of a publicly available set of single-cell RNA-sequencing data on bronchoalveolar lavage cells from patients with SARS-CoV-2 infection validated the double-sided role of MDMs. Blockade of inflammatory MDM recruitment using CCR2−/− mice effectively attenuates lung injury. Therefore, AMs and MDMs exhibited large differences during recovery. AMs are long-lived M2-like tissue-resident macrophages that have a strong ability to proliferate and phagocytose. MDMs are a paradoxical group of macrophages that promote the repair of tissue damage despite being strongly pro-inflammatory early in infection, and they may undergo cell death as inflammation fades. Preventing the massive recruitment of inflammatory MDMs or promoting their transition to pro-repairing phenotype may be a new direction for the treatment of acute lung injury.
Abstract
In acute lung injury, two subsets of lung macrophages exist in the alveoli: tissue-resident alveolar macrophages (AMs) and monocyte-derived alveolar macrophages (MDMs). However, it is unclear whether these 2 subsets of macrophages have different functions and characteristics during the recovery phase. RNA-sequencing of AMs and MDMs from the recovery period of LPS-induced lung injury mice revealed their differences in proliferation, cell death, phagocytosis, inflammation and tissue repair. Using flow cytometry, we found that AMs showed a higher ability to proliferate, whereas MDMs expressed a larger amount of cell death. We also compared the ability of phagocytosing apoptotic cells and activating adaptive immunity and found that AMs have a stronger ability to phagocytose, while MDMs are the cells that activate lymphocytes during the resolving phase. By testing surface markers, we found that MDMs were more prone to the M1 phenotype, but expressed a higher level of pro-repairing genes. Finally, analysis of a publicly available set of single-cell RNA-sequencing data on bronchoalveolar lavage cells from patients with SARS-CoV-2 infection validated the double-sided role of MDMs. Blockade of inflammatory MDM recruitment using CCR2−/− mice effectively attenuates lung injury. Therefore, AMs and MDMs exhibited large differences during recovery. AMs are long-lived M2-like tissue-resident macrophages that have a strong ability to proliferate and phagocytose. MDMs are a paradoxical group of macrophages that promote the repair of tissue damage despite being strongly pro-inflammatory early in infection, and they may undergo cell death as inflammation fades. Preventing the massive recruitment of inflammatory MDMs or promoting their transition to pro-repairing phenotype may be a new direction for the treatment of acute lung injury.
참고문헌 (34)
- Meyer NJ, "Acute respiratory distress syndrome", Lancet, 398, pp.622~637 (2021)
- Soni S, "Alveolar macrophage-derived microvesicles mediate acute lung injury", Thorax, 71, pp.1020~1029 (2016)
- Aggarwal NR, "Diverse macrophage populations mediate acute lung inflammation and resolution", Am J Physiol Lung Cell Mol Physiol, 306, pp.L709~L725 (2014)
- Hou F, "Diversity of macrophages in lung homeostasis and diseases", Front Immunol, 12, pp.753940~ (2021)
- Gomez Perdiguero E, "Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors", Nature, 518, pp.547~551 (2015)
- Guilliams M, "Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF", J Exp Med, 210, pp.1977~1992 (2013)
- Broug-Holub E, "Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia : elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival", Infect Immun, 65, pp.1139~1146 (1997)
- Byrne AJ, "Pulmonary macrophages : key players in the innate defence of the airways", Thorax, 70, pp.1189~1196 (2015)
- Herold S, "Acute lung injury : how macrophages orchestrate resolution of inflammation and tissue repair", Front Immunol, 2, pp.65~ (2011)
- Watanabe S, "The role of macrophages in the resolution of inflammation", J Clin Invest, 129, pp.2619~2628 (2019)
- Grégoire M, "Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS", Eur Respir J, 52, pp.1702590~ (2018)
- Doran AC, "Efferocytosis in health and disease", Nat Rev Immunol, 20, pp.254~267 (2020)
- Aegerter H, "Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection", Nat Immunol, 21, pp.145~157 (2020)
- Svedberg FR, "The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation", Nat Immunol, 20, pp.571~580 (2019)
- Hashimoto D, "Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes", Immunity, 38, pp.792~804 (2013)
- Zhu B, "Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection", Immunity, 54, pp.1200~1218 (2021)
- Neupane AS, "Patrolling alveolar macrophages conceal bacteria from the immune system to maintain homeostasis", Cell, 183, pp.110~125 (2020)
- Wynn TA, "Macrophages in tissue repair, regeneration, and fibrosis", Immunity, 44, pp.450~462 (2016)
- Ortega-Gómez A, "Resolution of inflammation : an integrated view", EMBO Mol Med, 5, pp.661~674 (2013)
- Dal-Secco D, "A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury", J Exp Med, 212, pp.447~456 (2015)
- Yang W, "Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair", Nat Commun, 10, pp.1076~ (2019)
- Liao M, "Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19", Nat Med, 26, pp.842~844 (2020)
- Mould KJ, "Cell origin dictates programming of resident versus recruited macrophages during acute lung injury", Am J Respir Cell Mol Biol, 57, pp.294~306 (2017)
- Janssen WJ, "Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury", Am J Respir Crit Care Med, 184, pp.547~560 (2011)
- Huynh ML, "Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation", J Clin Invest, 109, pp.41~50 (2002)
- Fadok VA, "Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine", paracrine mechanisms involving TGF-beta, PGE2, and PAF, 1998, pp.101, 890~898
- Gerlach BD, "Efferocytosis induces macrophage proliferation to help resolve tissue injury", Cell Metab, 33, pp.2445~2463 (2021)
- Schif-Zuck S, "Saturated-efferocytosis generates pro-resolving CD11b low macrophages : modulation by resolvins and glucocorticoids", Eur J Immunol, 41, pp.366~379 (2011)
- Van Dyken SJ, "Interleukin-4-and interleukin-13-mediated alternatively activated macrophages : roles in homeostasis and disease", Annu Rev Immunol, 31, pp.317~343 (2013)
- Minutti CM, "Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver", Science, 356, pp.1076~1080 (2017)
- Dhaliwal K, "Monocytes control second-phase neutrophil emigration in established lipopolysaccharide-induced murine lung injury", Am J Respir Crit Care Med, 186, pp.514~524 (2012)
- Junqueira C, "FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation", Nature, 606, pp.576~584 (2022)
- Merad M, "Pathological inflammation in patients with COVID-19 : a key role for monocytes and macrophages", Nat Rev Immunol, 20, pp.355~362 (2020)
- Misharin AV, "Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span", J Exp Med, 214, pp.2387~2404 (2017)