Eosinophils in Health and Disease: A State-of-the-Art Review

[en] Eosinophils play a homeostatic role in the body's immune responses. These cells are involved in combating some parasitic, bacterial, and viral infections and certain cancers and have pathologic roles in diseases including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic gastrointestinal disorders, and hypereosinophilic syndromes. Treatment of eosinophilic diseases has traditionally been through nonspecific eosinophil attenuation by use of glucocorticoids. However, several novel biologic therapies targeting eosinophil maturation factors, such as interleukin (IL)-5 and the IL-5 receptor or IL-4/IL-13, have recently been approved for clinical use. Despite the success of biologic therapies, some patients with eosinophilic inflammatory disease may not achieve adequate symptom control, underlining the need to further investigate the contribution of patient characteristics, such as comorbidities and other processes, in driving ongoing disease activity. New research has shown that eosinophils are also involved in several homeostatic processes, including metabolism, tissue remodeling and development, neuronal regulation, epithelial and microbiome regulation, and immunoregulation, indicating that these cells may play a crucial role in metabolic regulation and organ function in healthy humans. Consequently, further investigation is needed into the homeostatic roles of eosinophils and eosinophil-mediated processes across different tissues and their varied microenvironments. Such work may provide important insights into the role of eosinophils not only under disease conditions but also in health. This narrative review synthesizes relevant publications retrieved from PubMed informed by author expertise to provide new insights into the diverse roles of eosinophils in health and disease, with particular emphasis on the implications for current and future development of eosinophil-targeted therapies. © 2021 The Authors

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

Wechsler, M.E.; Department of Medicine, National Jewish Health, Denver, CO, United States

Munitz, A.; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Ackerman, S.J.; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago

Drake, M.G.; Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland

Jackson, D.J.; Guy's Severe Asthma Centre, Guy's and St Thomas’ NHS Trust, London, United Kingdom, Asthma UK Centre, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom

Wardlaw, A.J.; Institute for Lung Health, University of Leicester, Leicester, United Kingdom

Dougan, S.K.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, United States

Berdnikovs, S.; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Schleich, FLorence ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie

Matucci, A.; Immunoallergology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy

More authors (5 more)

Language :

English

Title :

Eosinophils in Health and Disease: A State-of-the-Art Review

Publication date :

2021

Journal title :

Mayo Clinic Proceedings

ISSN :

0025-6196

Publisher :

Elsevier Ltd

Volume :

Issue :

Pages :

2694 - 2707

Peer reviewed :

Peer Reviewed verified by ORBi

Funding text :

Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing, and referencing) was provided by Laura Gardner, PhD, CMPP, at Fishawack Indicia Ltd, United Kingdom, part of Fishawack Health, and was funded by GlaxoSmithKline .

Available on ORBi :

since 25 November 2022

Statistics

Number of views

27 (0 by ULiège)

Number of downloads

151 (1 by ULiège)

More statistics

Scopus citations^®

102

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Klion, A.D., Ackerman, S.J., Bochner, B.S., Contributions of eosinophils to human health and disease. Annu Rev Pathol 15 (2020), 179–209.
Abdala-Valencia, H., Coden, M.E., Chiarella, S.E., et al. Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease. J Leukoc Biol 104:1 (2018), 95–108.
McBrien, C.N., Menzies-Gow, A., The biology of eosinophils and their role in asthma. Front Med (Lausanne), 4, 2017, 93.
Robinson, D., Humbert, M., Buhl, R., et al. Revisiting type 2–high and type 2–low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy 47:2 (2017), 161–175.
Klion, A., Recent advances in understanding eosinophil biology. F1000Res, 6, 2017, 1084.
Acharya, K.R., Ackerman, S.J., Eosinophil granule proteins: form and function. J Biol Chem 289:25 (2014), 17406–17415.
Loktionov, A., Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders. World J Gastroenterol 25:27 (2019), 3503–3526.
Ueki, S., Tokunaga, T., Melo, R.C.N., et al. Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death. Blood 132:20 (2018), 2183–2187.
Melo, R.C., Weller, P.F., Piecemeal degranulation in human eosinophils: a distinct secretion mechanism underlying inflammatory responses. Histol Histopathol 25:10 (2010), 1341–1354.
Persson, E.K., Verstraete, K., Heyndrickx, I., et al. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. Science, 364(6442), 2019, eaaw4295.
Ackerman, S.J., Kephart, G.M., Francis, H., Awadzi, K., Gleich, G.J., Ottesen, E.A., Eosinophil degranulation. An immunologic determinant in the pathogenesis of the Mazzotti reaction in human onchocerciasis. J Immunol 144:10 (1990), 3961–3969.
Flores-Torres, A.S., Salinas-Carmona, M.C., Salinas, E., Rosas-Taraco, A.G., Eosinophils and respiratory viruses. Viral Immunol 32:5 (2019), 198–207.
Brigger, D., Riether, C., van Brummelen, R., et al. Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age. Nat Metab 2:8 (2020), 688–702.
Drake, M.G., Lebold, K.M., Roth-Carter, Q.R., et al. Eosinophil and airway nerve interactions in asthma. J Leukoc Biol 104:1 (2018), 61–67.
Weller, P.F., Spencer, L.A., Functions of tissue-resident eosinophils. Nat Rev Immunol 17:12 (2017), 746–760.
Mesnil, C., Raulier, S., Paulissen, G., et al. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest 126:9 (2016), 3279–3295.
Lavin, Y., Winter, D., Blecher-Gonen, R., et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:6 (2014), 1312–1326.
Hartl, S., Breyer, M.K., Burghuber, O.C., et al. Blood eosinophil count in the general population: typical values and potential confounders. Eur Respir J, 55(5), 2020, 1901874.
Castro, M., Corren, J., Pavord, I.D., et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 378:26 (2018), 2486–2496.
Castro, M., Zangrilli, J., Wechsler, M.E., et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials [erratum appears in Lancet Respir Med. 2015;3(4):e15]. Lancet Respir Med 3:5 (2015), 355–366.
FitzGerald, J.M., Bleecker, E.R., Nair, P., et al. Benralizumab, an anti–interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 388:10056 (2016), 2128–2141.
Ortega, H.G., Liu, M.C., Pavord, I.D., et al. Mepolizumab treatment in patients with severe eosinophilic asthma [erratum appears in N Engl J Med. 2015;372(18):1777]. N Engl J Med 371:13 (2014), 1198–1207.
Humbert, M., Beasley, R., Ayres, J., et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 60:3 (2005), 309–316.
Bachert, C., Han, J.K., Desrosiers, M., et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials [erratum appears in Lancet. 2019;394(10209):1618]. Lancet 394:10209 (2019), 1638–1650.
Gevaert, P., Omachi, T.A., Corren, J., et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials [erratum appears in J Allergy Clin Immunol. 2021;147(1):416]. J Allergy Clin Immunol 146:3 (2020), 595–605.
Hopkins, C., Bachert, C., Fokkens, W., et al. Add-on mepolizumab for chronic rhinosinusitis with nasal polyps: SYNAPSE study. Eur Respir J, 56(suppl 64), 2020, 4616.
Pavord, I.D., Chanez, P., Criner, G.J., et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med 377:17 (2017), 1613–1629.
Criner, G.J., Celli, B.R., Singh, D., et al. Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies. Lancet Respir Med 8:2 (2020), 158–170.
Wechsler, M.E., Akuthota, P., Jayne, D., et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med 376:20 (2017), 1921–1932.
Guntur, V.P., Manka, L., Denson, J.L., et al. Benralizumab as a steroid-sparing treatment option in eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol Pract 9:3 (2021), 1186–1193.e1.
Roufosse, F., Kahn, J.E., Rothenberg, M.E., et al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol 146:6 (2020), 1397–1405.
Kuang, F.L., Legrand, F., Makiya, M., et al. Benralizumab for PDGFRA-negative hypereosinophilic syndrome. N Engl J Med 380:14 (2019), 1336–1346.
Straumann, A., Conus, S., Grzonka, P., et al. Anti–interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 59:1 (2010), 21–30.
Spergel, J.M., Rothenberg, M.E., Collins, M.H., et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 129:2 (2012), 456–463 463.e1-3.
Hirano, I., Dellon, E.S., Hamilton, J.D., et al. Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis. Gastroenterology 158:1 (2020), 111–122.e10.
Hirano, I., Collins, M.H., Assouline-Dayan, Y., et al. RPC4046, a monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients with eosinophilic esophagitis. Gastroenterology 156:3 (2019), 592–603.e10.
Hirano, I., Peterson, K., Murray, J., et al. AK002, an anti–siglec-8 antibody, depletes tissue eosinophils and improves dysphagia symptoms in patients with eosinophilic esophagitis. J Allergy Clin Immunol, 145(2, suppl), 2020, AB167.
Dellon, E.S., Peterson, K.A., Murray, J.A., et al. Anti–siglec-8 antibody for eosinophilic gastritis and duodenitis. N Engl J Med 383:17 (2020), 1624–1634.
Pelaia, C., Paoletti, G., Puggioni, F., et al. Interleukin-5 in the pathophysiology of severe asthma. Front Physiol, 10, 2019, 1514.
Khatri, S., Moore, W., Gibson, P.G., et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol 143:5 (2019), 1742–1751.e7.
Murphy, K., Jacobs, J., Bjermer, L., et al. Long-term safety and efficacy of reslizumab in patients with eosinophilic asthma [erratum appears in J Allergy Clin Immunol Pract. 2018;6(3):1095]. J Allergy Clin Immunol Pract 5:6 (2017), 1572–1581.e3.
Fabre, V., Beiting, D.P., Bliss, S.K., et al. Eosinophil deficiency compromises parasite survival in chronic nematode infection. J Immunol 182:3 (2009), 1577–1583.
Kung, T.T., Stelts, D.M., Zurcher, J.A., et al. Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti–IL-5 antibody. Am J Respir Cell Mol Biol 13:3 (1995), 360–365.
Mauser, P.J., Pitman, A.M., Fernandez, X., et al. Effects of an antibody to interleukin-5 in a monkey model of asthma. Am J Respir Crit Care Med 152:2 (1995), 467–472.
O'Connell, A.E., Hess, J.A., Santiago, G.A., et al. Major basic protein from eosinophils and myeloperoxidase from neutrophils are required for protective immunity to Strongyloides stercoralis in mice. Infect Immun 79:7 (2011), 2770–2778.
Swartz, J.M., Dyer, K.D., Cheever, A.W., et al. Schistosoma mansoni infection in eosinophil lineage–ablated mice. Blood 108:7 (2006), 2420–2427.
Chung, K.F., Wenzel, S.E., Brozek, J.L., et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma [erratum appears in Eur Respir J. 2014;43(4):1216]. Eur Respir J 43:2 (2014), 343–373.
Yancey, S.W., Keene, O.N., Albers, F.C., et al. Biomarkers for severe eosinophilic asthma. J Allergy Clin Immunol 140:6 (2017), 1509–1518.
Price, D.B., Rigazio, A., Campbell, J.D., et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med 3:11 (2015), 849–858.
Szefler, S.J., Wenzel, S., Brown, R., et al. Asthma outcomes: biomarkers. J Allergy Clin Immunol 129:3, suppl (2012), S9–S23.
Pavord, I.D., Blood eosinophil-directed management of airway disease. The past, present, and future. Am J Respir Crit Care Med 202:5 (2020), 637–639.
Harvey, E.S., Langton, D., Katelaris, C., et al. Mepolizumab effectiveness and identification of super-responders in severe asthma. Eur Respir J, 55(5), 2020, 1902420.
Schleich, F.N., Chevremont, A., Paulus, V., et al. Importance of concomitant local and systemic eosinophilia in uncontrolled asthma. Eur Respir J 44:1 (2014), 97–108.
Nyenhuis, S.M., Alumkal, P., Du, J., Maybruck, B.T., Vinicky, M., Ackerman, S.J., Charcot-Leyden crystal protein/galectin-10 is a surrogate biomarker of eosinophilic airway inflammation in asthma. Biomark Med 13:9 (2019), 715–724.
Mukherjee, M., Aleman Paramo, F., Kjarsgaard, M., et al. Weight-adjusted intravenous reslizumab in severe asthma with inadequate response to fixed-dose subcutaneous mepolizumab. Am J Respir Crit Care Med 197:1 (2018), 38–46.
Howarth, P., Quirce, S., Papi, A., et al. Eosinophil-derived neurotoxin and clinical outcomes with mepolizumab in severe eosinophilic asthma. Allergy 75:8 (2020), 2085–2088.
Wardlaw, A., Howarth, P.H., Israel, E., et al. Fungal sensitization and its relationship to mepolizumab response in patients with severe eosinophilic asthma. Clin Exp Allergy 50:7 (2020), 869–872.
Schleich, F., Vaia, E.S., Pilette, C., et al. Mepolizumab for allergic bronchopulmonary aspergillosis: report of 20 cases from the Belgian Severe Asthma Registry and review of the literature. J Allergy Clin Immunol Pract 8:7 (2020), 2412–2413.e2.
Brenard, E., Pilette, C., Dahlqvist, C., et al. Real-life study of mepolizumab in idiopathic chronic eosinophilic pneumonia. Lung 198:2 (2020), 355–360.
Grozdanovic, M.M., Doyle, C.B., Liu, L., et al. Charcot-Leyden crystal protein/galectin-10 interacts with cationic ribonucleases and is required for eosinophil granulogenesis. J Allergy Clin Immunol 146:2 (2020), 377–389.e10.
Dunican, E.M., Elicker, B.M., Gierada, D.S., et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest 128:3 (2018), 997–1009.
Wu, D., Yan, B., Wang, Y., Zhang, L., Wang, C., Charcot-Leyden crystal concentration in nasal secretions predicts clinical response to glucocorticoids in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 144:1 (2019), 345–348.e8.
Curtis, C., Ogbogu, P., Hypereosinophilic syndrome. Clin Rev Allergy Immunol 50:2 (2016), 240–251.
Furuta, S., Iwamoto, T., Nakajima, H., Update on eosinophilic granulomatosis with polyangiitis. Allergol Int 68:4 (2019), 430–436.
Gioffredi, A., Maritati, F., Oliva, E., Buzio, C., Eosinophilic granulomatosis with polyangiitis: an overview. Front Immunol, 5, 2014, 549.
Steinfeld, J., Bradford, E.S., Brown, J., et al. Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol 143:6 (2019), 2170–2177.
Latorre, M., Novelli, F., Baldini, C., et al. Different disease subtypes in allergic eosinophilic granulomatosis with polyangiitis (EGPA). Eur Respir J, 42(suppl), 2013, 1797.
Egan, M., Furuta, G.T., Eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis. Ann Allergy Asthma Immunol 121:2 (2018), 162–167.
Varricchi, G., Galdiero, M.R., Loffredo, S., et al. Eosinophils: the unsung heroes in cancer?. Oncoimmunology, 7(2), 2018, e1393134.
Grisaru-Tal, S., Itan, M., Klion, A.D., Munitz, A., A new dawn for eosinophils in the tumour microenvironment. Nat Rev Cancer 20:10 (2020), 594–607.
Reichman, H., Itan, M., Rozenberg, P., et al. Activated eosinophils exert antitumorigenic activities in colorectal cancer. Cancer Immunol Res 7:3 (2019), 388–400.
Carretero, R., Sektioglu, I.M., Garbi, N., Salgado, O.C., Beckhove, P., Hämmerling, G.J., Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8+ T cells [erratum appears in Nat Immunol. 2016;17(2):214]. Nat Immunol 16:6 (2015), 609–617.
Dougan, M., Dranoff, G., Dougan, S.K., GM-CSF, IL-3, and IL-5 family of cytokines: regulators of inflammation. Immunity 50:4 (2019), 796–811.
Schuijs, M.J., Png, S., Richard, A.C., et al. ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung. Nat Immunol 21:9 (2020), 998–1009.
Sabogal Piñeros, Y.S., Bal, S.M., Dijkhuis, A., et al. Eosinophils capture viruses, a capacity that is defective in asthma. Allergy 74:10 (2019), 1898–1909.
Sabogal Piñeros, Y.S., Bal, S.M., van de Pol, M.A., et al. Anti–IL-5 in mild asthma alters rhinovirus-induced macrophage, B-cell, and neutrophil responses (MATERIAL). A placebo-controlled, double-blind study. Am J Respir Crit Care Med 199:4 (2019), 508–517.
Hatchwell, L., Collison, A., Girkin, J., et al. Toll-like receptor 7 governs interferon and inflammatory responses to rhinovirus and is suppressed by IL-5–induced lung eosinophilia. Thorax 70:9 (2015), 854–861.
Broadhurst, R., Peterson, R., Wisnivesky, J.P., et al. Asthma in COVID-19 hospitalizations: an overestimated risk factor?. Ann Am Thorac Soc 17:12 (2020), 1645–1648.
Godar, M., Deswarte, K., Vergote, K., et al. A bispecific antibody strategy to target multiple type 2 cytokines in asthma. J Allergy Clin Immunol 142:4 (2018), 1185–1193.e4.
Lee, J.J., Jacobsen, E.A., Ochkur, S.I., et al. Human versus mouse eosinophils: "that which we call an eosinophil, by any other name would stain as red". J Allergy Clin Immunol 130:3 (2012), 572–584.