Lung Interstitial Macrophages: Past, Present, and Future

[en] For a long time, investigations about the lung myeloid compartment have been mainly limited to the macrophages located within the airways, that is, the well-known alveolar macrophages specialized in recycling of surfactant molecules and removal of debris. However, a growing number of reports have highlighted the complexity of the lung myeloid compartment, which also encompass different subsets of dendritic cells, tissue monocytes, and nonalveolar macrophages, called interstitial macrophages (IM). Recent evidence supports that, in mice, IM perform important immune functions, including the maintenance of lung homeostasis and prevention of immune-mediated allergic airway inflammation. In this article, we describe lung IM from a historical perspective and we review current knowledge on their characteristics, ontogeny, and functions, mostly in rodents. Finally, we emphasize some important future challenges for the field.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Schyns, Joey ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire

Bureau, Fabrice ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire

Marichal, Thomas ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire

Language :

English

Title :

Lung Interstitial Macrophages: Past, Present, and Future

Publication date :

11 March 2018

Journal title :

Journal of Immunology Research

ISSN :

2314-8861

eISSN :

2314-7156

Publisher :

Hindawi Publishing Corporation, Egypt

Special issue title :

Macrophage Functions and Regulation: Roles in Diseases and Implications in Therapeutics

Volume :

2018

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 06 June 2018

Statistics

Number of views

122 (21 by ULiège)

Number of downloads

122 (9 by ULiège)

More statistics

Scopus citations^®

118

Scopus citations^®
without self-citations

112

OpenCitations

OpenAlex citations

129

Bibliography

M. H. Kaplan, A. H. Coons, and H. W. Deane, “Localization of antigen in tissue cells; cellular distribution of pneumococcal polysaccharides types II and III in the mouse,” Journal of Experimental Medicine, vol. 91, no. 1, pp. 15–30, 1949.
R. van Furth and Z. A. Cohn, “The origin and kinetics of mononuclear phagocytes,” Journal of Experimental Medicine, vol. 128, no. 3, pp. 415–435, 1968.
D. H. Bowden and I. Y. Adamson, “The pulmonary interstitial cell as immediate precursor of the alveolar macrophage,” The American Journal of Pathology, vol. 68, no. 3, pp. 521–537, 1972.
A. Blussé van Oud Alblas, B. van der Linden-Schrever, and R. van Furth, “Origin and kinetics of pulmonary macrophages during an inflammatory reaction induced by intravenous administration of heat-killed bacillus Calmette-Guerin,” The Journal of Experimental Medicine, vol. 154, no. 2, pp. 235–252, 1981.
Y. Cai, C. Sugimoto, M. Arainga, X. Alvarez, E. S. Didier, and M. J. Kuroda, “In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: implications for understanding lung disease in humans,” The Journal of Immunology, vol. 192, no. 6, pp. 2821–2829, 2014.
L. Landsman and S. Jung, “Lung macrophages serve as obligatory intermediate between blood monocytes and alveolar macrophages,” The Journal of Immunology, vol. 179, no. 6, pp. 3488–3494, 2007.
P. G. Holt, A. Degebrodt, T. Venaille et al., “Preparation of interstitial lung cells by enzymatic digestion of tissue slices: preliminary characterization by morphology and performance in functional assays,” Immunology, vol. 54, no. 1, pp. 139–147, 1985.
A. B. van oud Alblas and R. van Furth, “Origin, kinetics, and characteristics of pulmonary macrophages in the normal steady state,” The Journal of Experimental Medicine, vol. 149, no. 6, pp. 1504–1518, 1979.
N. Bilyk, J. S. Mackenzie, J. M. Papadimitriou, and P. G. Holt, “Functional studies on macrophage populations in the airways and the lung wall of SPF mice in the steady-state and during respiratory virus infection,” Immunology, vol. 65, no. 3, pp. 417–425, 1988.
A. R. Brody, J. C. Bonner, L. H. Overby et al., “Interstitial pulmonary macrophages produce platelet-derived growth factor that stimulates rat lung fibroblast proliferation in vitro,” Journal of Leukocyte Biology, vol. 51, no. 6, pp. 640–648, 1992.
D. B. Drath, P. Davies, J. M. Shorey, N. S. Gibran, P. J. Simpson, and G. L. Huber, “Characterization of a postlavage, in situ pulmonary macrophage population,” Journal of Cellular Physiology, vol. 111, no. 1, pp. 97–103, 1982.
C. A. Rouzer, W. A. Scott, A. L. Hamill, and Z. A. Cohn, “Synthesis of leukotriene C and other arachidonic acid metabolites by mouse pulmonary macrophages,” The Journal of Experimental Medicine, vol. 155, no. 3, pp. 720–733, 1982.
C. Steinmüller, G. Franke-Ullmann, M. L. Lohmann-Matthes, and A. Emmendörffer, “Local activation of nonspecific defense against a respiratory model infection by application of interferon-gamma: comparison between rat alveolar and interstitial lung macrophages,” American Journal of Respiratory Cell and Molecular Biology, vol. 22, no. 4, pp. 481–490, 2000.
A. Johansson, M. Lundborg, C. M. Sköld et al., “Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages,” American Journal of Respiratory Cell and Molecular Biology, vol. 16, no. 5, pp. 582–588, 1997.
D. B. Chandler, J. I. Kennedy, and J. D. Fulmer, “Studies of membrane receptors, phagocytosis, and morphology of subpopulations of rat lung interstitial macrophages,” The American Review of Respiratory Disease, vol. 134, no. 3, pp. 542–547, 1986.
G. Franke-Ullmann, C. Pförtner, P. Walter, C. Steinmüller, M. L. Lohmann-Matthes, and L. Kobzik, “Characterization of murine lung interstitial macrophages in comparison with alveolar macrophages in vitro,” The Journal of Immunology, vol. 157, no. 7, pp. 3097–3104, 1996.
M. Lagranderie, M. A. Nahori, A. M. Balazuc et al., “Dendritic cells recruited to the lung shortly after intranasal delivery of Mycobacterium bovis BCG drive the primary immune response towards a type 1 cytokine production,” Immunology, vol. 108, no. 3, pp. 352–364, 2003.
D. L. Laskin, B. Weinberger, and J. D. Laskin, “Functional heterogeneity in liver and lung macrophages,” Journal of Leukocyte Biology, vol. 70, no. 2, pp. 163–170, 2001.
A. J. Byrne, T. M. Maher, and C. M. Lloyd, “Pulmonary macrophages: a new therapeutic pathway in fibrosing lung disease?,” Trends in Molecular Medicine, vol. 22, no. 4, pp. 303–316, 2016.
M. Guilliams, I. de Kleer, S. Henri et al., “Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF,” The Journal of Experimental Medicine, vol. 210, no. 10, pp. 1977–1992, 2013.
S. Y. S. Tan and M. A. Krasnow, “Developmental origin of lung macrophage diversity,” Development, vol. 143, no. 8, pp. 1318–1327, 2016.
R. E. Crowell, E. Heaphy, Y. E. Valdez, C. Mold, and B. E. Lehnert, “Alveolar nd interstitial macrophage populations in the murine lung,” Experimental Lung Research, vol. 18, no. 4, pp. 435–446, 2009.
L. Kobzik, J. J. Godleski, B. E. Barry, and J. D. Brain, “Isolation and antigenic identification of hamster lung interstitial macrophages,” The American Review of Respiratory Disease, vol. 138, no. 4, pp. 908–914, 1988.
B. E. Lehnert, Y. E. Valdez, and L. M. Holland, “Pulmonary macrophages: alveolar and interstitial populations,” Experimental Lung Research, vol. 9, no. 3-4, pp. 177–190, 2009.
C. Jakubzick, E. L. Gautier, S. L. Gibbings et al., “Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes,” Immunity, vol. 39, no. 3, pp. 599–610, 2013.
C. Sabatel, C. Radermecker, L. Fievez et al., “Exposure to bacterial CpG DNA protects from airway allergic inflammation by expanding regulatory lung interstitial macrophages,” Immunity, vol. 46, no. 3, pp. 457–473, 2017.
Y. Okabe and R. Medzhitov, “Tissue biology perspective on macrophages,” Nature Immunology, vol. 17, no. 1, pp. 9–17, 2016.
R. J. Sebring and B. E. Lehnert, “Morphometric comparisons of rat alveolar macrophages, pulmonary interstitial macrophages, and blood monocytes,” Experimental Lung Research, vol. 18, no. 4, pp. 479–496, 2009.
A. V. Misharin, L. Morales-Nebreda, G. M. Mutlu, G. R. S. Budinger, and H. Perlman, “Flow cytometric analysis of macrophages and dendritic cell subsets in the mouse lung,” American Journal of Respiratory Cell and Molecular Biology, vol. 49, no. 4, pp. 503–510, 2013.
B. Becher, A. Schlitzer, J. Chen et al., “High-dimensional analysis of the murine myeloid cell system,” Nature Immunology, vol. 15, no. 12, pp. 1181–1189, 2014.
S. L. Gibbings, S. M. Thomas, S. M. Atif et al., “Three unique interstitial macrophages in the murine lung at steady state,” American Journal of Respiratory Cell and Molecular Biology, vol. 57, no. 1, pp. 66–76, 2017.
D. Bedoret, H. Wallemacq, T. Marichal et al., “Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice,” The Journal of Clinical Investigation, vol. 119, no. 12, pp. 3723–3738, 2009.
T. Tschernig and R. Pabst, “What is the clinical relevance of different lung compartments?,” BMC Pulmonary Medicine, vol. 9, no. 1, p. 39, 2009.
S. Epelman, K. J. Lavine, and G. J. Randolph, “Origin and functions of tissue macrophages,” Immunity, vol. 41, no. 1, pp. 21–35, 2014.
F. Ginhoux and M. Guilliams, “Tissue-resident macrophage ontogeny and homeostasis,” Immunity, vol. 44, no. 3, pp. 439–449, 2016.
M. Guilliams and C. L. Scott, “Does niche competition determine the origin of tissue-resident macrophages?,” Nature Reviews Immunology, vol. 17, no. 7, pp. 451–460, 2017.
F. Ginhoux, M. Greter, M. Leboeuf et al., “Fate mapping analysis reveals that adult microglia derive from primitive macrophages,” Science, vol. 330, no. 6005, pp. 841–845, 2010.
I. M. Samokhvalov, N. I. Samokhvalova, and S.-I. Nishikawa, “Cell tracing shows the contribution of the yolk sac to adult haematopoiesis,” Nature, vol. 446, no. 7139, pp. 1056–1061, 2007.
E. Gomez Perdiguero, K. Klapproth, C. Schulz et al., “Tissue-resident macrophages originate from yolk-sac-derived erythromyeloid progenitors,” Nature, vol. 518, no. 7540, pp. 547–551, 2015.
D. Hashimoto, A. Chow, C. Noizat et al., “Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes,” Immunity, vol. 38, no. 4, pp. 792–804, 2013.
S. Yona, K. W. Kim, Y. Wolf et al., “Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis,” Immunity, vol. 38, no. 1, pp. 79–91, 2013.
C. C. Bain, A. Bravo-Blas, C. L. Scott et al., “Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice,” Nature Immunology, vol. 15, no. 10, pp. 929–937, 2014.
S. Tamoutounour, M. Guilliams, F. Montanana Sanchis et al., “Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin,” Immunity, vol. 39, no. 5, pp. 925–938, 2013.
S. Epelman, K. J. Lavine, A. E. Beaudin et al., “Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation,” Immunity, vol. 40, no. 1, pp. 91–104, 2014.
N. V. Serbina and E. G. Pamer, “Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2,” Nature Immunology, vol. 7, no. 3, pp. 311–317, 2006.
D. B. Chandler, G. Bayles, and W. C. Fuller, “Prostaglandin synthesis and release by subpopulations of rat interstitial macrophages,” The American Review of Respiratory Disease, vol. 138, no. 4, pp. 901–907, 1988.
D. B. Chandler and A. L. Brannen, “Interstitial macrophage subpopulations: responsiveness to chemotactic stimuli,” Tissue and Cell, vol. 22, no. 4, pp. 427–434, 1990.
H. Bouabe, Y. Liu, M. Moser, M. R. Bösl, and J. Heesemann, “Novel highly sensitive IL-10-β-lactamase reporter mouse reveals cells of the innate immune system as a substantial source of IL-10 in vivo,” The Journal of Immunology, vol. 187, no. 6, pp. 3165–3176, 2011.
N. A-Gonzalez, J. A. Quintana, S. García-Silva et al., “Phagocy-tosis imprints heterogeneity in tissue-resident macrophages,” The Journal of Experimental Medicine, vol. 214, no. 5, pp. 1281–1296, 2017.
H. Kawano, H. Kayama, T. Nakama, T. Hashimoto, E. Umemoto, and K. Takeda, “IL-10-producing lung interstitial macrophages prevent neutrophilic asthma,” International Immunology, vol. 28, no. 10, pp. 489–501, 2016.
P. L. Brazee, P. N. Soni, E. Tokhtaeva et al., “FXYD5 is an essential mediator of the inflammatory response during lung injury,” Frontiers in Immunology, vol. 8, p. 623, 2017.
S. C. Pugliese, S. Kumar, W. J. Janssen et al., “A time- and compartment-specific activation of lung macrophages in hypoxic pulmonary hypertension,” The Journal of Immunology, vol. 198, no. 12, pp. 4802–4812, 2017.
M. Toussaint, L. Fievez, P. V. Drion et al., “Myeloid hypoxia-inducible factor 1α prevents airway allergy in mice through macrophage-mediated immunoregulation,” Mucosal Immunology, vol. 6, no. 3, pp. 485–497, 2013.
M. Fathi, A. Johansson, M. Lundborg, L. Orre, C. M. Sköld, and P. Camner, “Functional and morphological differences between human alveolar and interstitial macrophages,” Experimental and Molecular Pathology, vol. 70, no. 2, pp. 77–82, 2001.
J. L. Gong, K. M. McCarthy, R. A. Rogers, and E. E. Schneeberger, “Interstitial lung macrophages interact with dendritic cells to present antigenic peptides derived from particulate antigens to T cells,” Immunology, vol. 81, no. 3, pp. 343–351, 1994.
J. Hoppstädter, B. Diesel, R. Zarbock et al., “Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages,” Respiratory Research, vol. 11, no. 1, 2010.
S. C. Eisenbarth, D. A. Piggott, J. W. Huleatt, I. Visintin, C. A. Herrick, and K. Bottomly, “Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen,” The Journal of Experimental Medicine, vol. 196, no. 12, pp. 1645–1651, 2002.
H. Hammad, M. Chieppa, F. Perros, M. A. Willart, R. N. Germain, and B. N. Lambrecht, “House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells,” Nature Medicine, vol. 15, no. 4, pp. 410–416, 2009.
C. Mesnil, C. M. Sabatel, T. Marichal et al., “Resident CD11b+-Ly6C− lung dendritic cells are responsible for allergic airway sensitization to house dust mite in mice,” PLoS One, vol. 7, no. 12, article e53242, 2012.
M. Plantinga, M. Guilliams, M. Vanheerswynghels et al., “Conventional and monocyte-derived CD11b+ dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen,” Immunity, vol. 38, no. 2, pp. 322–335, 2013.
C. Mesnil, S. Raulier, G. Paulissen et al., “Lung-resident eosinophils represent a distinct regulatory eosinophil subset,” The Journal of Clinical Investigation, vol. 126, no. 9, pp. 3279–3295, 2016.
C. Braun-Fahrländer, J. Riedler, U. Herz et al., “Environmental exposure to endotoxin and its relation to asthma in school-age children,” The New England Journal of Medicine, vol. 347, no. 12, pp. 869–877, 2002.
S. R. Roy, A. M. Schiltz, A. Marotta, Y. Shen, and A. H. Liu, “Bacterial DNA in house and farm barn dust,” The Journal of Allergy and Clinical Immunology, vol. 112, no. 3, pp. 571–578, 2003.
D. P. Strachan, “Hay fever, hygiene, and household size,” BMJ, vol. 299, no. 6710, pp. 1259-1260, 1989.
E. von Mutius, “The microbial environment and its influence on asthma prevention in early life,” The Journal of Allergy and Clinical Immunology, vol. 137, no. 3, pp. 680–689, 2016.
K. M. Beeh, F. Kanniess, F. Wagner et al., “The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma,” The Journal of Allergy and Clinical Immunology, vol. 131, no. 3, pp. 866–874, 2013.
D. Broide, J. Schwarze, H. Tighe et al., “Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice,” The Journal of Immunology, vol. 161, pp. 7054–7062, 1998.
P. S. Creticos, J. T. Schroeder, R. G. Hamilton et al., “Immuno-therapy with a ragweed-Toll-like receptor 9 agonist vaccine for allergic rhinitis,” The New England Journal of Medicine, vol. 355, no. 14, pp. 1445–1455, 2006.
J. N. Kline, T. J. Waldschmidt, T. R. Businga et al., “Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma,” The Journal of Immunology, vol. 160, no. 6, pp. 2555–2559, 1998.
A. M. Krieg, “CpG still rocks! Update on an accidental drug,” Nucleic Acid Therapeutics, vol. 22, no. 2, pp. 77–89, 2012.
S. Sur, J. S. Wild, B. K. Choudhury, N. Sur, R. Alam, and D. M. Klinman, “Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides,” The Journal of Immunology, vol. 162, pp. 6284–6293, 1999.
J. D. Crapo, B. E. Barry, P. Gehr, M. Bachofen, and E. R. Weibel, “Cell number and cell characteristics of the normal human lung,” The American Review of Respiratory Disease, vol. 126, no. 2, pp. 332–337, 1982.
G. S. Davis, A. R. Brody, and J. E. Craighead, “Analysis of airspace and interstitial mononuclear cell populations in human diffuse interstitial lung disease,” The American Review of Respiratory Disease, vol. 118, no. 1, pp. 7–15, 1978.
J. C. Weissler, C. R. Lyons, M. F. Lipscomb, and G. B. Toews, “Human pulmonary macrophages. Functional comparison of cells obtained from whole lung and by bronchoalveolar lavage,” The American Review of Respiratory Disease, vol. 133, no. 3, pp. 473–477, 1986.
S. Ferrari-Lacraz, L. P. Nicod, R. Chicheportiche, H. G. Welgus, and J. M. Dayer, “Human lung tissue macrophages, but not alveolar macrophages, express matrix metalloproteinases after direct contact with activated T lymphocytes,” American Journal of Respiratory Cell and Molecular Biology, vol. 24, no. 4, pp. 442–451, 2001.
C. Draijer, C. E. Boorsma, P. Robbe et al., “Human asthma is characterized by more IRF5+ M1 and CD206+ M2 macrophages and less IL-10+ M2-like macrophages around airways compared with healthy airways,” The Journal of Allergy and Clinical Immunology, vol. 140, no. 1, pp. 280–283.e3, 2017.
A. Bharat, S. M. Bhorade, L. Morales-Nebreda et al., “Flow cytometry reveals similarities between lung macrophages in humans and mice,” American Journal of Respiratory Cell and Molecular Biology, vol. 54, no. 1, pp. 147–149, 2016.
A. N. Desch, S. L. Gibbings, R. Goyal et al., “Flow cytometric analysis of mononuclear phagocytes in nondiseased human lung and lung-draining lymph nodes,” American Journal of Respiratory and Critical Care Medicine, vol. 193, no. 6, pp. 614–626, 2016.
Y.-R. A. Yu, D. F. Hotten, Y. Malakhau et al., “Flow cytometric analysis of myeloid cells in human blood, bronchoalveolar lavage, and lung tissues,” American Journal of Respiratory Cell and Molecular Biology, vol. 54, no. 1, pp. 13–24, 2016.
J. A. Dewhurst, S. Lea, E. Hardaker, J. V. Dungwa, A. K. Ravi, and D. Singh, “Characterisation of lung macrophage subpopulations in COPD patients and controls,” Scientific Reports, vol. 7, no. 1, p. 7143, 2017.
A. Giladi and I. Amit, “Immunology, one cell at a time,” Nature, vol. 547, no. 7661, pp. 27–29, 2017.
K. E. Neu, Q. Tang, P. C. Wilson, and A. A. Khan, “Single-cell genomics: approaches and utility in immunology,” Trends in Immunology, vol. 38, no. 2, pp. 140–149, 2017.