The interstitial macrophage: A long-neglected piece in the puzzle of lung immunity

[en] Lung macrophages have mostly been studied considering only their most accessible and well-de fined representative, the alveolar macrophage (AM). In contrast, the identity and putative immune functions of their tissue counterpart, the interstitial macrophage (IM), have long remained much more elusive. Yet, recent evidence supports the notion that IMs perform important immune functions in the lung, notably in terms of innate immunoregulation. Here, we review current knowledge on the phenotype, ontogeny and function of IMs and propose strategies for the unambiguous identification and study of this important and dynamic lung innate immune cell population

Disciplines :

Biochemistry, biophysics & molecular biology
Veterinary medicine & animal health

Author, co-author :

Liégeois, Maude ^✱; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire

Legrand, Céline ^✱; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire

Desmet, Christophe ^✱; 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

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

^✱ These authors have contributed equally to this work.

Language :

English

Title :

The interstitial macrophage: A long-neglected piece in the puzzle of lung immunity

Publication date :

2018

Journal title :

Cellular Immunology

ISSN :

0008-8749

eISSN :

1090-2163

Publisher :

Elsevier, Atlanta, United States - Florida

Volume :

330

Pages :

91-96

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

WELBIO - Institut wallon virtuel de recherche d'excellence dans les domaines des sciences de la vie
F.R.S.-FNRS - Fonds de la Recherche Scientifique
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture
Fondation Acteria (Agir sur la Recherche européenne en Immunologie et en Allergologie)

Available on ORBi :

since 18 April 2018

Statistics

Number of views

174 (50 by ULiège)

Number of downloads

6 (5 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

108

Bibliography

Balhara, J., Gounni, A.S., The alveolar macrophages in asthma: a double-edged sword. Mucosal Immunol. 5 (2012), 605–609.
Hussell, T., Bell, T.J., Alveolar macrophages: plasticity in a tissue-specific context. Nat. Rev. Immunol. 14 (2014), 81–93.
Byrne, A.J., Mathie, S.A., Gregory, L.G., Lloyd, C.M., Pulmonary macrophages: key players in the innate defence of the airways. Thorax 70 (2015), 1189–1196.
Lehnert, B.E., Valdez, Y.E., Holland, L.M., Pulmonary macrophages: alveolar and interstitial populations. Exp. Lung Res. 9 (1985), 177–190.
Holt, P.G., Degebrodt, A., Venaille, T., O'Leary, C., Krska, K., Flexman, J., Farrell, H., Shellam, G., Young, P., Penhale, J., Preparation of interstitial lung cells by enzymatic digestion of tissue slices: preliminary characterization by morphology and performance in functional assays. Immunology 54 (1985), 139–147.
Bedoret, D., Wallemacq, H., Marichal, T., Desmet, C., Calvo, F.Q., Henry, E., Closset, R., Dewals, B., Thielen, C., Gustin, P., De Leval, L., Van Rooijen, N., Le Moine, A., Vanderplasschen, A., Cataldo, D., Drion, P.V., Moser, M., Lekeux, P., Bureau, F., Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. J. Clin. Invest. 119 (2009), 3723–3738.
Hoppstadter, J., Diesel, B., Zarbock, R., Breinig, T., Monz, D., Koch, M., Meyerhans, A., Gortner, L., Lehr, C.M., Huwer, H., Kiemer, A.K., Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages. Respir. Res., 11, 2010, 124.
Cai, Y., Sugimoto, C., Arainga, M., Alvarez, X., Didier, E.S., Kuroda, M.J., In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: implications for understanding lung disease in humans. J. Immunol. 192 (2014), 2821–2829.
Blussé van Oud Alblas, A., van der Linden-Schrever, B., van Furth, R., Origin and kinetics of pulmonary macrophages during an inflammatory reaction induced by intravenous administration of heat-killed bacillus Calmette-Guérin. J. Exp. Med. 154 (1981), 235–252.
Koch, C.M., Chiu, S.F., Misharin, A.V., Ridge, K.M., Lung interstitial macrophages: establishing identity and uncovering heterogeneity. Am. J. Respir. Cell Mol. Biol. 57 (2017), 7–9.
Landsman, L., Jung, S., Lung macrophages serve as obligatory intermediate between blood monocytes and alveolar macrophages. J. Immunol. 179 (2007), 3488–3494.
Misharin, A.V., Scott Budinger, G.R., Perlman, H., The lung macrophage: a Jack of all trades. Am. J. Respir. Crit. Care Med. 184 (2011), 497–498.
Toussaint, M., Fievez, L., Drion, P.-V., Cataldo, D., Bureau, F., Lekeux, P., Desmet, C.J., Myeloid hypoxia-inducible factor 1α prevents airway allergy in mice through macrophage-mediated immunoregulation. Mucosal Immunol. 6 (2013), 485–497.
Sabatel, C., Radermecker, C., Fievez, L., Paulissen, G., Chakarov, S., Fernandes, C., Olivier, S., Toussaint, M., Pirottin, D., Xiao, X., Quatresooz, P., Sirard, J.-C., Cataldo, D., Gillet, L., Bouabe, H., Desmet, C.J., Ginhoux, F., Marichal, T., Bureau, F., Exposure to bacterial CpG DNA protects from airway allergic inflammation by expanding regulatory lung interstitial macrophages. Immunity 46 (2017), 457–473.
Yu, Y.-R.A., Hotten, D.F., Malakhau, Y., Volker, E., Ghio, A.J., Noble, P.W., Kraft, M., Hollingsworth, J.W., Gunn, M.D., Tighe, R.M., Flow cytometric analysis of myeloid cells in human blood, bronchoalveolar lavage, and lung tissues. Am. J. Respir. Cell Mol. Biol. 54 (2016), 13–24.
Jakubzick, C., Gautier, E.L., Gibbings, S.L., Sojka, D.K., Schlitzer, A., Johnson, T.E., Ivanov, S., Duan, Q., Bala, S., Condon, T., van Rooijen, N., Grainger, J.R., Belkaid, Y., Ma'ayan, A., Riches, D.W.H., Yokoyama, W.M., Ginhoux, F., Henson, P.M., Randolph, G.J., Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39 (2013), 599–610.
Desch, A.N., Gibbings, S.L., Goyal, R., Kolde, R., Bednarek, J., Bruno, T., Slansky, J.E., Jacobelli, J., Mason, R., Ito, Y., Messier, E., Randolph, G.J., Prabagar, M., Atif, S.M., Segura, E., Xavier, R.J., Bratton, D.L., Janssen, W.J., Henson, P.M., Jakubzick, C.V., Flow cytometric analysis of mononuclear phagocytes in nondiseased human lung and lung-draining lymph nodes. Am. J. Respir. Crit. Care Med. 193 (2016), 614–626.
Hanna, R.N., Carlin, L.M., Hubbeling, H.G., Nackiewicz, D., Green, A.M., Punt, J.A., Geissmann, F., Hedrick, C.C., The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes. Nat. Immunol. 12 (2011), 778–785.
Serbina, N.V., Pamer, E.G., Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol. 7 (2006), 311–317.
Mesnil, C., Raulier, S., Paulissen, G., Xiao, X., Birrell, M.A., Pirottin, D., Janss, T., Starkl, P., Ramery, E., Henket, M., Schleich, F.N., Radermecker, M., Thielemans, K., Gillet, L., Thiry, M., Belvisi, M.G., Louis, R., Desmet, C., Marichal, T., Bureau, F., Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J. Clin. Invest. 126 (2016), 3279–3295.
Gibbings, S.L., Thomas, S.M., Atif, S.M., McCubbrey, A.L., Desch, A.N., Danhorn, T., Leach, S.M., Bratton, D.L., Henson, P.M., Janssen, W.J., Jakubzick, C.V., Three unique interstitial macrophages in the murine lung at steady state. Am. J. Respir. Cell. Mol. Biol. 57 (2017), 66–76.
Guilliams, M., Ginhoux, F., Jakubzick, C., Naik, S.H., Onai, N., Schraml, B.U., Segura, E., Tussiwand, R., Yona, S., Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat. Rev. Immunol. 14 (2014), 571–578.
Tighe, R.M., Liang, J., Liu, N., Jung, Y., Jiang, D., Gunn, M.D., Noble, P.W., Recruited exudative macrophages selectively produce CXCL10 after noninfectious lung injury. Am. J. Respir. Cell. Mol. Biol. 45 (2011), 781–788.
Chung, Y., Hong, J.Y., Lei, J., Chen, Q., Bentley, J.K., Hershenson, M.B., Rhinovirus infection induces interleukin-13 production from CD11b-positive, M2-polarized exudative macrophages. Am. J. Respir. Cell. Mol. Biol. 52 (2014), 205–216.
Han, M., Chung, Y., Young Hong, J., Rajput, C., Lei, J., Hinde, J.L., Chen, Q., Weng, S.P., Bentley, J.K., Hershenson, M.B., Toll-like receptor 2–expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation. J. Allergy Clin. Immunol. 138 (2016), 1619–1630.
Bharat, A., Bhorade, S.M., Morales-Nebreda, L., McQuattie-Pimentel, A.C., Soberanes, S., Ridge, K., DeCamp, M.M., Mestan, K.K., Perlman, H., Budinger, G.R.S., Misharin, A.V., Flow cytometry reveals similarities between lung macrophages in humans and mice. Am. J. Respir. Cell. Mol. Biol. 54 (2016), 147–149.
Franke-Ullmann, G., Pfortner, C., Walter, P., Steinmuller, C., Lohmann-Matthes, M.L., Kobzik, L., Characterization of murine lung interstitial macrophages in comparison with alveolar macrophages in vitro. J. Immunol. 157 (1996), 3097–3104.
Zaynagetdinov, R., Sherrill, T.P., Kendall, P.L., Segal, B.H., Weller, K.P., Tighe, R.M., Blackwell, T.S., Identification of myeloid cell subsets in murine lungs using flow cytometry. Am. J. Respir. Cell. Mol. Biol. 49 (2013), 180–189.
Fathi, M., Johansson, A., Lundborg, M., Orre, L., Sköld, C.M., Camner, P., Functional and morphological differences between human alveolar and interstitial macrophages. Exp. Mol. Pathol. 70 (2001), 77–82.
Sebring, R.J., Lehnert, B.E., Morphometric comparisons of rat alveolar macrophages, pulmonary interstitial macrophages, and blood monocytes. Exp. Lung Res. 18 (1992), 479–496.
Wizemann, T.M., Laskin, D.L., Enhanced phagocytosis, chemotaxis, and production of reactive oxygen intermediates by interstitial lung macrophages following acute endotoxemia. Am. J. Respir. Cell. Mol. Biol. 11 (1994), 358–365.
Misharin, A.V., Morales-Nebreda, L., Mutlu, G.M., Budinger, G.R.S., Perlman, H., Flow cytometric analysis of macrophages and dendritic cell subsets in the mouse lung. Am. J. Respir. Cell. Mol. Biol. 49 (2013), 503–510.
Johansson, A., Lundborg, M., Sköld, C.M., Lundahl, J., Tornling, G., Eklund, A., Camner, P., Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages. Am. J. Respir. Cell Mol. Biol. 16 (1997), 582–588.
Gong, J.L., McCarthy, K.M., Rogers, R.A., Schneeberger, E.E., Interstitial lung macrophages interact with dendritic cells to present antigenic peptides derived from particulate antigens to T cells. Immunology 81 (1994), 343–351.
Kawano, H., Kayama, H., Nakama, T., Hashimoto, T., Umemoto, E., Takeda, K., IL-10-producing lung interstitial macrophages prevent neutrophilic asthma. Int. Immunol. 28 (2016), 489–501.
Braun-Fahrlander, C., Riedler, J., Herz, U., Eder, W., Waser, M., Grize, L., Maisch, S., Carr, D., Gerlach, F., Bufe, A., Lauener, R.P., Schierl, R., Renz, H., Nowak, D., von Mutius, E., Environmental exposure to endotoxin and its relation to asthma in school-age children. N. Engl. J. Med. 347 (2002), 869–877.
Roy, S.R., Schiltz, A.M., Marotta, A., Shen, Y., Liu, A.H., Bacterial DNA in house and farm barn dust. J. Allergy Clin. Immunol. 112 (2003), 571–578.
Strachan, D.P., Hay fever, hygiene, and household size. Br. Med. J. 299 (1989), 1259–1260.
von Mutius, E., Allergies, infections and the hygiene hypothesis–the epidemiological evidence. Immunobiology 212 (2007), 433–439.
Schuijs, M.J., Willart, M.A., Vergote, K., Gras, D., Deswarte, K., Ege, M.J., Madeira, F.B., Beyaert, R., van Loo, G., Bracher, F., von Mutius, E., Chanez, P., Lambrecht, B.N., Hammad, H., Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science 349 (2015), 1106–1110.
Kline, J.N., Krieg, A.M., Waldschmidt, T.J., Ballas, Z.K., Jain, V., Businga, T.R., CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma. J. Allergy Clin. Immunol. 104 (1999), 1258–1264.
Sur, S., Wild, J.S., Choudhury, B.K., Sur, N., Alam, R., Klinman, D.M., Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J. Immunol. 162 (1999), 6284–6293.
Creticos, P.S., Schroeder, J.T., Hamilton, R.G., Balcer-Whaley, S.L., Khattignavong, A.P., Lindblad, R., Li, H., Coffman, R., Seyfert, V., Eiden, J.J., Broide, D., Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N. Engl. J. Med. 355 (2006), 1445–1455.
Beeh, K.-M., Kanniess, F., Wagner, F., Schilder, C., Naudts, I., Hammann-Haenni, A., Willers, J., Stocker, H., Mueller, P., Bachmann, M.F., Renner, W.A., The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma. J. Allergy Clin Immunol. 131 (2013), 866–874.
Hashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M., Leboeuf, M., Becker, C., See, P., Price, J., Lucas, D., Greter, M., Mortha, A., Boyer, S., Camilla Forsberg, E., Tanaka, M., van Rooijen, N., GarcÌa-Sastre, A., Richard Stanley, E., Ginhoux, F., Frenette, P., Merad, M., Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38 (2013), 792–804.
Guilliams, M., De Kleer, I., Henri, S., Post, S., Vanhoutte, L., De Prijck, S., Deswarte, K., Malissen, B., Hammad, H., Lambrecht, B.N., 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 (2013), 1977–1992.
Kopf, M., Schneider, C., Nobs, S.P., The development and function of lung-resident macrophages and dendritic cells. Nat. Immunol. 16 (2014), 36–44.
Ginhoux, F., Guilliams, M., Tissue-resident macrophage ontogeny and homeostasis. Immunity 44 (2016), 439–449.
Maus, U.A., Janzen, S., Wall, G., Srivastava, M., Blackwell, T.S., Christman, J.W., Seeger, W., Welte, T., Lohmeyer, J., Resident alveolar macrophages are replaced by recruited monocytes in response to endotoxin-induced lung inflammation. Am. J. Respir. Cell. Mol. Biol. 35 (2006), 227–235.
Swirski, F.K., Nahrendorf, M., Etzrodt, M., Wildgruber, M., Cortez-Retamozo, V., Panizzi, P., Figueiredo, J.-L., Kohler, R.H., Chudnovskiy, A., Waterman, P., Aikawa, E., Mempel, T.R., Libby, P., Weissleder, R., Pittet, M.J., Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325 (2009), 612–616.
Pugliese, S.C., Kumar, S., Janssen, W.J., Graham, B.B., Frid, M.G., Riddle, S.R., El Kasmi, K.C., Stenmark, K.R., A time- and compartment-specific activation of lung macrophages in hypoxic pulmonary hypertension. J. Immunol. 198 (2017), 4802–4812.
Ginhoux, F., Jung, S., Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 14 (2014), 392–404.
Lavin, Y., Mortha, A., Rahman, A., Merad, M., Regulation of macrophage development and function in peripheral tissues. Nat. Rev. Immunol. 15 (2015), 731–744.
Nie, H., Wang, A., He, Q., Yang, Q., Liu, L., Zhang, G., Huang, Y., Ding, X., Yu, H., Hu, S., Phenotypic switch in lung interstitial macrophage polarization in an ovalbumin-induced mouse model of asthma. Exp. Ther. Med. 14 (2017), 1284–1292.
Draijer, C., Boorsma, C.E., Robbe, P., Timens, W., Hylkema, M.N., Ten Hacken, N.H., van den Berge, M., Postma, D.S., Melgert, B.N., 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. J. Allergy Clin. Immunol., 140, 2017 280.e3–283.e3.