Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-11T10:33:35.428Z Has data issue: false hasContentIssue false
  • English
  • Français

Alveolar macrophages: novel therapeutic targets for respiratory diseases

Published online by Cambridge University Press:  26 November 2021

Pamelia N. Lim Open the ORCID record for Pamelia N. Lim [Opens in a new window] ,
Maritza M. Cervantes Open the ORCID record for Maritza M. Cervantes [Opens in a new window] ,
Linh K. Pham Open the ORCID record for Linh K. Pham [Opens in a new window]  and
Alissa C. Rothchild Open the ORCID record for Alissa C. Rothchild [Opens in a new window]
Pamelia N. Lim
Affiliation:
Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA01003, USA Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA01003, USA
Maritza M. Cervantes
Affiliation:
Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA01003, USA
Linh K. Pham
Affiliation:
Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA01003, USA Graduate Program in Animal Biotechnology & Biomedical Sciences, University of Massachusetts Amherst, Amherst, MA01003, USA
Alissa C. Rothchild*
Affiliation:
Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA01003, USA
*
Author for correspondence: Alissa C. Rothchild, E-mail: arothchild@umass.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Alveolar macrophages (AMs) are lung-resident myeloid cells that sit at the interface of the airway and lung tissue. Under homeostatic conditions, their primary function is to clear debris, dead cells and excess surfactant from the airways. They also serve as innate pulmonary sentinels for respiratory pathogens and environmental airborne particles and as regulators of pulmonary inflammation. However, they have not typically been viewed as primary therapeutic targets for respiratory diseases. Here, we discuss the role of AMs in various lung diseases, explore the potential therapeutic strategies to target these innate cells and weigh the potential risks and challenges of such therapies. Additionally, in the context of the COVID-19 pandemic, we examine the role AMs play in severe disease and the therapeutic strategies that have been harnessed to modulate their function and protect against severe lung damage. There are many novel approaches in development to target AMs, such as inhaled antibiotics, liposomal and microparticle delivery systems, and host-directed therapies, which have the potential to provide critical treatment to patients suffering from severe respiratory diseases, yet there is still much work to be done to fully understand the possible benefits and risks of such approaches.

Keywords

Aerosol drug deliveryalveolar macrophageshost-directed therapiesinnate immunitylung biologymyeloid cellspulmonary inflammationrespiratory diseases
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e18
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Yona, S et al. (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91.CrossRefGoogle ScholarPubMed
Misharin, AV et al. (2017) Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. Journal of Experimental Medicine 214, 2387–2404.CrossRefGoogle ScholarPubMed
van de Laar, L et al. (2016) Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages. Immunity 44, 755–768.CrossRefGoogle ScholarPubMed
Mould, KJ et al. (2021) Airspace macrophages and monocytes exist in transcriptionally distinct subsets in healthy adults. American Journal of Respiratory and Critical Care Medicine 203, 946–956.CrossRefGoogle ScholarPubMed
McQuattie-Pimentel, AC et al. (2021) The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging. The Journal of Clinical Investigation 131, e140299.CrossRefGoogle Scholar
Gautier, EL et al. (2012) Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nature Immunology 13, 1118–1128.CrossRefGoogle ScholarPubMed
Lavin, Y et al. (2014) Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159, 1312–1326.CrossRefGoogle ScholarPubMed
Dranoff, G et al. (1994) Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science (New York, N.Y.) 264, 713–716.CrossRefGoogle ScholarPubMed
Trapnell, BC, Whitsett, JA and Nakata, K (2003) Pulmonary alveolar proteinosis. New England Journal of Medicine 349, 2527–2539.CrossRefGoogle ScholarPubMed
Malur, A et al. (2011) Restoration of PPARgamma reverses lipid accumulation in alveolar macrophages of GM-CSF knockout mice. American Journal of Physiology. Lung Cellular and Molecular Physiology 300, L73–L80.CrossRefGoogle ScholarPubMed
Schneider, C et al. (2014) Induction of the nuclear receptor PPAR-gamma by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nature Immunology 15, 1026–1037.CrossRefGoogle ScholarPubMed
Nakamura, A et al. (2013) Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function. Journal of Experimental Medicine 210, 2191–2204.CrossRefGoogle ScholarPubMed
Suwankitwat, N et al. (2021) The actin-regulatory protein Hem-1 is essential for alveolar macrophage development. Journal of Experimental Medicine 218, e20200472.CrossRefGoogle ScholarPubMed
Hussell, T and Bell, TJ (2014) Alveolar macrophages: plasticity in a tissue-specific context. Nature Reviews Immunology 14, 81–93.CrossRefGoogle Scholar
Gordon, SB et al. (2014) Respiratory risks from household air pollution in low and middle income countries. The Lancet. Respiratory medicine 2, 823–860.CrossRefGoogle ScholarPubMed
Shaddick, G et al. (2018) Data integration for the assessment of population exposure to ambient Air pollution for global burden of disease assessment. Environmental Science and Technology 52, 9069–9078.CrossRefGoogle ScholarPubMed
G. R. F. Collaborators (2020) Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet (London, England) 396, 1223–1249.CrossRefGoogle Scholar
Rothchild, AC et al. (2019) Alveolar macrophages generate a noncanonical NRF2-driven transcriptional response to Mycobacterium tuberculosis in vivo. Science Immunology 4, eaaw6693.CrossRefGoogle ScholarPubMed
Cohen, SB et al. (2018) Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host & Microbe 24, 439–446 e434.CrossRefGoogle ScholarPubMed
Mwandumba, HC et al. (2004) Mycobacterium tuberculosis resides in nonacidified vacuoles in endocytically competent alveolar macrophages from patients with tuberculosis and HIV infection. Journal of Immunology 172, 4592–4598.CrossRefGoogle ScholarPubMed
Lee, J et al. (2020) CD11cHi monocyte-derived macrophages are a major cellular compartment infected by Mycobacterium tuberculosis. PLoS Pathogens 16, e1008621.CrossRefGoogle ScholarPubMed
Huang, L et al. (2018) Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny. Journal of Experimental Medicine 215, 1135–1152.CrossRefGoogle ScholarPubMed
Liu, X et al. (2020) Legionella-infected macrophages engage the alveolar epithelium to metabolically reprogram myeloid cells and promote antibacterial inflammation. Cell Host & Microbe 28, 683–698 e686.CrossRefGoogle ScholarPubMed
Philippe, B et al. (2003) Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infection and Immunity 71, 3034–3042.CrossRefGoogle ScholarPubMed
Steiner, DJ et al. (2017) Protective role for macrophages in respiratory Francisella tularensis infection. Infection and Immunity 85, e00064–17.CrossRefGoogle ScholarPubMed
Allwood, EM et al. (2011) Strategies for intracellular survival of Burkholderia pseudomallei. Frontiers in Microbiology 2, 170.CrossRefGoogle ScholarPubMed
Snelgrove, RJ et al. (2008) A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nature Immunology 9, 1074–1083.CrossRefGoogle ScholarPubMed
Wong, CK et al. (2017) Aging impairs alveolar macrophage phagocytosis and increases influenza-induced mortality in mice. Journal of Immunology 199, 1060–1068.CrossRefGoogle ScholarPubMed
Santos, LD et al. (2021) TNF-mediated alveolar macrophage necroptosis drives disease pathogenesis during respiratory syncytial virus infection. European Respiratory Journal 57, 2003764.CrossRefGoogle ScholarPubMed
Liao, M et al. (2020) Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nature Medicine 26, 842–844.CrossRefGoogle ScholarPubMed
Lv, J et al. (2021) Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages. Cell Discovery 7, 24.CrossRefGoogle ScholarPubMed
Zhou, Z et al. (2020) Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host & Microbe 27, 883–890 e882.CrossRefGoogle ScholarPubMed
Nakajima, N et al. (2012) Histopathological and immunohistochemical findings of 20 autopsy cases with 2009 H1N1 virus infection. Modern Pathology 25, 1–13.CrossRefGoogle ScholarPubMed
Melms, JC et al. (2021) A molecular single-cell lung atlas of lethal COVID-19. Nature 595, 114–119.CrossRefGoogle ScholarPubMed
Kuiken, T et al. (2010) Comparative pathology of select agent influenza a virus infections. Veterinary Pathology 47, 893–914.CrossRefGoogle ScholarPubMed
Guarner, J and Falcon-Escobedo, R (2009) Comparison of the pathology caused by H1N1, H5N1, and H3N2 influenza viruses. Archives of Medical Research 40, 655–661.CrossRefGoogle ScholarPubMed
Schneider, C et al. (2014) Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. PLoS Pathogens 10, e1004053.CrossRefGoogle ScholarPubMed
Bansal, S et al. (2018) IL-1 Signaling prevents alveolar macrophage depletion during influenza and Streptococcus pneumoniae coinfection. Journal of Immunology 200, 1425–1433.CrossRefGoogle ScholarPubMed
Verma, AK et al. (2020) Influenza infection induces alveolar macrophage dysfunction and thereby enables noninvasive Streptococcus pneumoniae to cause deadly pneumonia. Journal of Immunology 205, 1601–1607.CrossRefGoogle ScholarPubMed
World Health Organization (2016) Ambient air pollution: a global assessment of exposure and burden of disease.CrossRefGoogle Scholar
Cho, CC et al. (2018) In vitro and in vivo experimental studies of PM2.5 on disease progression. International Journal of Environmental Research and Public Health 15, 1380.CrossRefGoogle ScholarPubMed
McClure, CD and Jaffe, DA (2018) US particulate matter air quality improves except in wildfire-prone areas. Proceedings of the National Academy of Sciences of the USA 115, 7901–7906.CrossRefGoogle ScholarPubMed
Alexis, NE et al. (2006) In vivo particle uptake by airway macrophages in healthy volunteers. American Journal of Respiratory Cell and Molecular Biology 34, 305–313.CrossRefGoogle ScholarPubMed
Geiser, M (2002) Morphological aspects of particle uptake by lung phagocytes. Microscopy Research and Technique 57, 512–522.CrossRefGoogle ScholarPubMed
Pinkerton, KE et al. (2000) Distribution of particulate matter and tissue remodeling in the human lung. Environmental Health Perspectives 108, 1063–1069.CrossRefGoogle ScholarPubMed
Miyata, R and van Eeden, SF (2011) The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter. Toxicology and Applied Pharmacology 257, 209–226.CrossRefGoogle ScholarPubMed
Rimal, B, Greenberg, AK and Rom, WN (2005) Basic pathogenetic mechanisms in silicosis: current understanding. Current Opinion in Pulmonary Medicine 11, 169–173.CrossRefGoogle ScholarPubMed
Srivastava, KD et al. (2002) Crucial role of interleukin-1beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice. American Journal of Respiratory and Critical Care Medicine 165, 527–533.CrossRefGoogle ScholarPubMed
Dostert, C et al. (2008) Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science (New York, N.Y.) 320, 674–677.CrossRefGoogle ScholarPubMed
Woodruff, PG et al. (2005) A distinctive alveolar macrophage activation state induced by cigarette smoking. American Journal of Respiratory and Critical Care Medicine 172, 1383–1392.CrossRefGoogle ScholarPubMed
Richens, TR et al. (2009) Cigarette smoke impairs clearance of apoptotic cells through oxidant-dependent activation of RhoA. American Journal of Respiratory and Critical Care Medicine 179, 1011–1021.CrossRefGoogle ScholarPubMed
Phipps, JC et al. (2010) Cigarette smoke exposure impairs pulmonary bacterial clearance and alveolar macrophage complement-mediated phagocytosis of Streptococcus pneumoniae. Infection and Immunity 78, 1214–1220.CrossRefGoogle ScholarPubMed
O'Leary, SM et al. (2014) Cigarette smoking impairs human pulmonary immunity to Mycobacterium tuberculosis. American Journal of Respiratory and Critical Care Medicine 190, 1430–1436.CrossRefGoogle ScholarPubMed
Gleeson, LE et al. (2018) Cigarette smoking impairs the bioenergetic immune response to Mycobacterium tuberculosis infection. American Journal of Respiratory Cell and Molecular Biology 59, 572–579.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention (2020) CDC, states update number of hospitalized EVALI cases and EVALI deaths. Available at https://www.cdc.gov/media/releases/2020/s0225-EVALI-cases-deaths.html.Google Scholar
Shields, PG et al. (2020) Lipid laden macrophages and electronic cigarettes in healthy adults. EBioMedicine 60, 102982.CrossRefGoogle ScholarPubMed
Vlahos, R and Bozinovski, S (2014) Role of alveolar macrophages in chronic obstructive pulmonary disease. Frontiers in Immunology 5, 435.CrossRefGoogle ScholarPubMed
Beckett, EL et al. (2013) A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis. Journal of Allergy and Clinical Immunology 131, 752–762.CrossRefGoogle ScholarPubMed
Weisberg, SP, Ural, BB and Farber, DL (2021) Tissue-specific immunity for a changing world. Cell 184, 1517–1529.CrossRefGoogle ScholarPubMed
Yao, Y et al. (2018) Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity. Cell 175, 1634–1650 e1617.CrossRefGoogle ScholarPubMed
Iwasaki, A and Medzhitov, R (2015) Control of adaptive immunity by the innate immune system. Nature Immunology 16, 343–353.CrossRefGoogle ScholarPubMed
Ruge, CA, Kirch, J and Lehr, CM (2013) Pulmonary drug delivery: from generating aerosols to overcoming biological barriers-therapeutic possibilities and technological challenges. The Lancet. Respiratory Medicine 1, 402–413.CrossRefGoogle ScholarPubMed
Gehr, P, Bachofen, M and Weibel, ER (1978) The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respiration Physiology 32, 121–140.CrossRefGoogle ScholarPubMed
Szabo, PA et al. (2021) Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19. Immunity 54, 797–814 e796.CrossRefGoogle ScholarPubMed
Lee, WH et al. (2015) Nano- and micro-based inhaled drug delivery systems for targeting alveolar macrophages. Expert Opinion on Drug Delivery 12, 1009–1026.CrossRefGoogle ScholarPubMed
Patel, B, Gupta, N and Ahsan, F (2015) Particle engineering to enhance or lessen particle uptake by alveolar macrophages and to influence the therapeutic outcome. European Journal of Pharmaceutics and Biopharmaceutics 89, 163–174.CrossRefGoogle ScholarPubMed
Edwards, DA and Dunbar, C (2002) Bioengineering of therapeutic aerosols. Annual Review of Biomedical Engineering 4, 93–107.CrossRefGoogle ScholarPubMed
Edwards, DA et al. (1997) Large porous particles for pulmonary drug delivery. Science (New York, N.Y.) 276, 1868–1871.CrossRefGoogle ScholarPubMed
Kelly, C, Jefferies, C and Cryan, SA (2011) Targeted liposomal drug delivery to monocytes and macrophages. Journal of Drug Delivery 2011, 727241.CrossRefGoogle ScholarPubMed
Lawlor, C et al. (2011) The application of high-content analysis in the study of targeted particulate delivery systems for intracellular drug delivery to alveolar macrophages. Molecular Pharmaceutics 8, 1100–1112.CrossRefGoogle Scholar
Arredouani, MS et al. (2005) MARCO is the major binding receptor for unopsonized particles and bacteria on human alveolar macrophages. Journal of Immunology 175, 6058–6064.CrossRefGoogle Scholar
Palecanda, A et al. (1999) Role of the scavenger receptor MARCO in alveolar macrophage binding of unopsonized environmental particles. Journal of Experimental Medicine 189, 1497–1506.CrossRefGoogle ScholarPubMed
Kulkarni, A et al. (2018) A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer. Nature Biomedical Engineering 2, 589–599.CrossRefGoogle ScholarPubMed
Ramesh, A et al. (2019) CSF1R- and SHP2-inhibitor-loaded nanoparticles enhance cytotoxic activity and phagocytosis in tumor-associated macrophages. Advanced Materials 31, e1904364.CrossRefGoogle ScholarPubMed
Nemeth, J et al. (2020) Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection. PLoS Pathogens 16, e1008655.CrossRefGoogle ScholarPubMed
Kaufmann, E et al. (2018) BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176–190 e119.CrossRefGoogle ScholarPubMed
Khan, N et al. (2020) M. tuberculosis reprograms hematopoietic stem cells to limit myelopoiesis and impair trained immunity. Cell 183, 752–770 e722.CrossRefGoogle ScholarPubMed
Netea, MG et al. (2020) Defining trained immunity and its role in health and disease. Nature Reviews Immunology 20, 375–388.CrossRefGoogle ScholarPubMed
Khader, SA et al. (2019) Targeting innate immunity for tuberculosis vaccination. The Journal of Clinical Investigation 129, 3482–3491.CrossRefGoogle ScholarPubMed
Quon, BS, Goss, CH and Ramsey, BW (2014) Inhaled antibiotics for lower airway infections. Annals of the American Thoracic Society 11, 425–434.CrossRefGoogle ScholarPubMed
Wenzler, E et al. (2016) Inhaled antibiotics for gram-negative respiratory infections. Clinical Microbiology Reviews 29, 581–632.CrossRefGoogle ScholarPubMed
Leoung, GS et al. (1990) Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial. New England Journal of Medicine 323, 769–775.CrossRefGoogle ScholarPubMed
Wassermann, K et al. (1991) Pentamidine aerosol increases the number of alveolar macrophages in HIV-infected patients. AIDS (London, England) 5, 1099–1102.CrossRefGoogle ScholarPubMed
Koziel, H et al. (1998) Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation. The Journal of Clinical Investigation 102, 1332–1344.CrossRefGoogle ScholarPubMed
Braunstein, M, Hickey, AJ and Ekins, S (2019) Why wait? The case for treating tuberculosis with inhaled drugs. Pharmaceutical Research 36, 166.CrossRefGoogle ScholarPubMed
Cicchese, JM et al. (2020) Both pharmacokinetic variability and granuloma heterogeneity impact the ability of the first-line antibiotics to sterilize tuberculosis granulomas. Frontiers in Pharmacology 11, 333.CrossRefGoogle ScholarPubMed
Patton, JS and Byron, PR (2007) Inhaling medicines: delivering drugs to the body through the lungs. Nature Reviews. Drug Discovery 6, 67–74.CrossRefGoogle ScholarPubMed
Chavas, TEJ et al. (2021) A macrophage-targeted platform for extending drug dosing with polymer prodrugs for pulmonary infection prophylaxis. Journal of Controlled Release 330, 284–292.CrossRefGoogle ScholarPubMed
Zhang, J et al. (2018) Amikacin liposome inhalation suspension (ALIS) penetrates non-tuberculous mycobacterial biofilms and enhances amikacin uptake into macrophages. Frontiers in Microbiology 9, 915.CrossRefGoogle ScholarPubMed
Hamblin, KA et al. (2017) Inhaled liposomal ciprofloxacin protects against a lethal infection in a murine model of pneumonic plague. Frontiers in Microbiology 8, 91.CrossRefGoogle Scholar
Sharma, R et al. (2011) Inhalable microparticles modify cytokine secretion by lung macrophages of infected mice. Tuberculosis (Edinb) 91, 107–110.CrossRefGoogle ScholarPubMed
Gyongyosi, A et al. (2013) RDH10, RALDH2, and CRABP2 are required components of PPARgamma-directed ATRA synthesis and signaling in human dendritic cells. Journal of Lipid Research 54, 2458–2474.CrossRefGoogle ScholarPubMed
Huang, S et al. (2019) PPAR-gamma in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection. Journal of Virology 93, e00030–19.CrossRefGoogle ScholarPubMed
Yoon, YS et al. (2015) PPARgamma activation following apoptotic cell instillation promotes resolution of lung inflammation and fibrosis via regulation of efferocytosis and proresolving cytokines. Mucosal Immunology 8, 1031–1046.CrossRefGoogle ScholarPubMed
Rajaram, MV et al. (2010) Mycobacterium tuberculosis activates human macrophage peroxisome proliferator-activated receptor gamma linking mannose receptor recognition to regulation of immune responses. Journal of Immunology 185, 929–942.CrossRefGoogle ScholarPubMed
Guirado, E et al. (2018) Deletion of PPARgamma in lung macrophages provides an immunoprotective response against M. tuberculosis infection in mice. Tuberculosis (Edinb) 111, 170–177.CrossRefGoogle ScholarPubMed
Petrina, M, Martin, J and Basta, S (2021) Granulocyte macrophage colony-stimulating factor has come of age: from a vaccine adjuvant to antiviral immunotherapy. Cytokine & Growth Factor Reviews 59, 101–110.CrossRefGoogle ScholarPubMed
Lang, FM et al. (2020) GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nature Reviews Immunology 20, 507–514.CrossRefGoogle ScholarPubMed
Huang, FF et al. (2011) GM-CSF in the lung protects against lethal influenza infection. American Journal of Respiratory and Critical Care Medicine 184, 259–268.CrossRefGoogle ScholarPubMed
Naessens, T et al. (2016) GM-CSF treatment prevents respiratory syncytial virus-induced pulmonary exacerbation responses in postallergic mice by stimulating alveolar macrophage maturation. Journal of Allergy and Clinical Immunology 137, 700–709 e709.CrossRefGoogle ScholarPubMed
Herold, S et al. (2014) Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine 189, 609–611.CrossRefGoogle ScholarPubMed
De Luca, G et al. (2020) GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study. Lancet Rheumatology 2, e465–e473.CrossRefGoogle ScholarPubMed
Vaine, CA and Soberman, RJ (2014) The CD200-CD200R1 inhibitory signaling pathway: immune regulation and host-pathogen interactions. Advances in Immunology 121, 191–211.CrossRefGoogle ScholarPubMed
Mahadevan, D et al. (2019) Phase I study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: blockade of the immune checkpoint CD200. Journal for Immunotherapy of Cancer 7, 227.CrossRefGoogle ScholarPubMed
Boutten, A et al. (2011) NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease. Trends in Molecular Medicine 17, 363–371.CrossRefGoogle ScholarPubMed
Rangasamy, T et al. (2004) Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. The Journal of Clinical Investigation 114, 1248–1259.CrossRefGoogle ScholarPubMed
Zhao, H et al. (2017) The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury. American Journal of Physiology. Lung Cellular and Molecular Physiology 312, L155–L162.CrossRefGoogle ScholarPubMed
Andrade, BB et al. (2015) Heme oxygenase-1 regulation of matrix metalloproteinase-1 expression underlies distinct disease profiles in tuberculosis. Journal of Immunology 195, 2763–2773.CrossRefGoogle ScholarPubMed
Scharn, CR et al. (2016) Heme oxygenase-1 regulates inflammation and mycobacterial survival in human macrophages during Mycobacterium tuberculosis infection. Journal of Immunology 196, 4641–4649.CrossRefGoogle ScholarPubMed
Reddy, NM et al. (2009) Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in mice. Journal of Immunology 182, 7264–7271.CrossRefGoogle ScholarPubMed
Grabiec, AM and Hussell, T (2016) The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation. Seminars in Immunopathology 38, 409–423.CrossRefGoogle ScholarPubMed
Liu, G et al. (2008) High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine. Journal of Immunology 181, 4240–4246.CrossRefGoogle ScholarPubMed
Ogden, CA et al. (2001) C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. Journal of Experimental Medicine 194, 781–795.CrossRefGoogle ScholarPubMed
Hodge, S et al. (2006) Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages. European Respiratory Journal 28, 486–495.CrossRefGoogle ScholarPubMed
Coleman, MM et al. (2018) All-trans retinoic acid augments autophagy during intracellular bacterial infection. American Journal of Respiratory Cell and Molecular Biology 59, 548–556.CrossRefGoogle ScholarPubMed
O'Connor, G et al. (2019) Inhalable poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating all-trans-retinoic acid (ATRA) as a host-directed, adjunctive treatment for Mycobacterium tuberculosis infection. European Journal of Pharmaceutics and Biopharmaceutics 134, 153–165.CrossRefGoogle ScholarPubMed
Singh, P and Subbian, S (2018) Harnessing the mTOR pathway for tuberculosis treatment. Frontiers in Microbiology 9, 70.CrossRefGoogle ScholarPubMed
Gupta, A et al. (2014) Inhalable particles containing rapamycin for induction of autophagy in macrophages infected with Mycobacterium tuberculosis. Molecular Pharmaceutics 11, 1201–1207.CrossRefGoogle ScholarPubMed
Wallis, RS et al. (2021) Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial. The Lancet. Respiratory medicine 9, 897–908.CrossRefGoogle ScholarPubMed
Vandenbroucke, RE, Dejonckheere, E and Libert, C (2011) A therapeutic role for matrix metalloproteinase inhibitors in lung diseases? European Respiratory Journal 38, 1200–1214.CrossRefGoogle ScholarPubMed
Kaner, RJ, Santiago, F and Crystal, RG (2009) Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1(+) smokers with early emphysema. Journal of Leukocyte Biology 86, 913–922.CrossRefGoogle ScholarPubMed
Cox, DJ et al. (2020) Inhibiting histone deacetylases in human macrophages promotes glycolysis, IL-1beta, and T helper cell responses to Mycobacterium tuberculosis. Frontiers in Immunology 11, 1609.CrossRefGoogle Scholar
Cosio, BG et al. (2004) Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. Journal of Experimental Medicine 200, 689–695.CrossRefGoogle ScholarPubMed
Abdulnour, RE et al. (2016) Aspirin-triggered resolvin D1 is produced during self-resolving gram-negative bacterial pneumonia and regulates host immune responses for the resolution of lung inflammation. Mucosal Immunology 9, 1278–1287.CrossRefGoogle ScholarPubMed
Hsiao, HM et al. (2013) A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation. PLoS ONE 8, e58258.CrossRefGoogle ScholarPubMed
Codagnone, M et al. (2018) Resolvin D1 enhances the resolution of lung inflammation caused by long-term Pseudomonas aeruginosa infection. Mucosal Immunology 11, 35–49.CrossRefGoogle ScholarPubMed
Li, D et al. (2014) IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice. Journal of Allergy and Clinical Immunology 134, 1422–1432 e1411.CrossRefGoogle ScholarPubMed
Wang, CC et al. (2021) Airborne transmission of respiratory viruses. Science (New York, N.Y.) 373, eabd9149.CrossRefGoogle ScholarPubMed
Cevik, M et al. (2020) Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 371, m3862.CrossRefGoogle ScholarPubMed
Grant, RA et al. (2021) Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. Nature 590, 635–641.CrossRefGoogle Scholar
Bost, P et al. (2020) Host-viral infection maps reveal signatures of severe COVID-19 patients. Cell 181, 1475–1488 e1412.CrossRefGoogle ScholarPubMed
Wang, C et al. (2020) Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. EBioMedicine 57, 102833.CrossRefGoogle ScholarPubMed
Abassi, Z et al. (2020) The lung macrophage in SARS-CoV-2 infection: a friend or a foe? Frontiers in Immunology 11, 1312.CrossRefGoogle ScholarPubMed
Merad, M and Martin, JC (2020) Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nature Reviews Immunology 20, 355–362.CrossRefGoogle ScholarPubMed
Schneider, JL et al. (2021) The aging lung: physiology, disease, and immunity. Cell 184, 1990–2019.CrossRefGoogle Scholar
Hadjadj, J et al. (2020) Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science (New York, N.Y.) 369, 718–724.CrossRefGoogle ScholarPubMed
Blanco-Melo, D et al. (2020) Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 1036–1045 e1039.CrossRefGoogle ScholarPubMed
Carvalho, T, Krammer, F and Iwasaki, A (2021) The first 12 months of COVID-19: a timeline of immunological insights. Nature Reviews Immunology 21, 245–256.CrossRefGoogle ScholarPubMed
Park, A and Iwasaki, A (2020) Type I and type III interferons – induction, signaling, evasion, and application to combat COVID-19. Cell Host & Microbe 27, 870–878.CrossRefGoogle ScholarPubMed
Zhang, Q et al. (2020) Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science (New York, N.Y.) 370, eabd4570.CrossRefGoogle ScholarPubMed
Lu, Q et al. (2021) SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2. Immunity 54, 1304–1319.CrossRefGoogle ScholarPubMed
Su, Y et al. (2020) Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19. Cell 183, 1479–1495 e1420.CrossRefGoogle ScholarPubMed
Mann, ER et al. (2020) Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19. Science Immunology 5, eabd6197.CrossRefGoogle ScholarPubMed
Liu, L et al. (2019) Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 4, e123158.CrossRefGoogle ScholarPubMed
Hamilton, JA (2020) GM-CSF in inflammation. Journal of Experimental Medicine 217, e20190945.CrossRefGoogle ScholarPubMed
Netea, MG et al. (2020) Trained immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection. Cell 181, 969–977.CrossRefGoogle ScholarPubMed
Forbes, B et al. (2014) Challenges for inhaled drug discovery and development: induced alveolar macrophage responses. Advanced Drug Delivery Reviews 71, 15–33.CrossRefGoogle ScholarPubMed