Myeloid-derived Suppressor Cells in Influenza Virus-induced Asthma Exacerbation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 May 2

PMID 38694499

Authors

Chiel van Geffen

Tim Lange

Saeed Kolahian

Affiliations

Soon will be listed here.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a phenotypically heterogenous group of cells that potently suppress the immune response. A growing body of evidence supports the important role of MDSCs in a variety of lung diseases, such as asthma. However, the role of MDSCs in asthma exacerbation has so far not been investigated. Here, we studied the role of MDSCs in a murine model of influenza virus-induced asthma exacerbation. BALB/c mice were exposed to house dust mite (HDM) three times a week for a total of five weeks to induce a chronic asthmatic phenotype, which was exacerbated by additional exposure to the A/Hamburg/5/2009 hemagglutinin 1 neuraminidase 1 (H1N1) influenza virus. Induction of lung inflammatory features, production of T helper (Th) 1- and Th2- associated inflammatory cytokines in the lavage fluid and an increased airway hyper-responsiveness were observed, establishing the asthma exacerbation model. The number and activity of pulmonary M-MDSCs increased in exacerbated asthmatic mice compared to non-exacerbated asthmatic mice. Furthermore, depletion of MDSCs aggravated airway hyper-responsiveness in exacerbated asthmatic mice. These findings further denote the role of MDSCs in asthma and provide some of the first evidence supporting a potential important role of MDSCs in asthma exacerbation.

References

Li H, Wang H, Sokulsky L, Liu S, Yang R, Liu X . Single-cell transcriptomic analysis reveals key immune cell phenotypes in the lungs of patients with asthma exacerbation. J Allergy Clin Immunol. 2020; 147(3):941-954. DOI: 10.1016/j.jaci.2020.09.032. View

Gabriel G, Klingel K, Otte A, Thiele S, Hudjetz B, Arman-Kalcek G . Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus. Nat Commun. 2011; 2:156. PMC: 3105303. DOI: 10.1038/ncomms1158. View

Castillo J, Peters S, Busse W . Asthma Exacerbations: Pathogenesis, Prevention, and Treatment. J Allergy Clin Immunol Pract. 2017; 5(4):918-927. PMC: 5950727. DOI: 10.1016/j.jaip.2017.05.001. View

Boomer J, Parulekar A, Patterson B, Yin-DeClue H, Deppong C, Crockford S . A detailed phenotypic analysis of immune cell populations in the bronchoalveolar lavage fluid of atopic asthmatics after segmental allergen challenge. Allergy Asthma Clin Immunol. 2013; 9(1):37. PMC: 3848528. DOI: 10.1186/1710-1492-9-37. View

Gerlach T, Kuhling L, Uhlendorff J, Laukemper V, Matrosovich T, Czudai-Matwich V . Characterization of the neuraminidase of the H1N1/09 pandemic influenza virus. Vaccine. 2012; 30(51):7348-52. DOI: 10.1016/j.vaccine.2012.09.078. View

Takeyama Y, Kato M, Tamada S, Azuma Y, Shimizu Y, Iguchi T . Myeloid-derived suppressor cells are essential partners for immune checkpoint inhibitors in the treatment of cisplatin-resistant bladder cancer. Cancer Lett. 2020; 479:89-99. DOI: 10.1016/j.canlet.2020.03.013. View

Suzuki E, Kapoor V, Jassar A, Kaiser L, Albelda S . Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005; 11(18):6713-21. DOI: 10.1158/1078-0432.CCR-05-0883. View

Miller R, Grayson M, Strothman K . Advances in asthma: New understandings of asthma's natural history, risk factors, underlying mechanisms, and clinical management. J Allergy Clin Immunol. 2021; 148(6):1430-1441. DOI: 10.1016/j.jaci.2021.10.001. View

Aun M, Bonamichi-Santos R, Arantes-Costa F, Kalil J, Giavina-Bianchi P . Animal models of asthma: utility and limitations. J Asthma Allergy. 2017; 10:293-301. PMC: 5683778. DOI: 10.2147/JAA.S121092. View

10.

Johnson J, Wiley R, Fattouh R, Swirski F, Gajewska B, Coyle A . Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. Am J Respir Crit Care Med. 2003; 169(3):378-85. DOI: 10.1164/rccm.200308-1094OC. View

11.

De Santo C, Salio M, Masri S, Lee L, Dong T, Speak A . Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J Clin Invest. 2008; 118(12):4036-48. PMC: 2582442. DOI: 10.1172/JCI36264. View

12.

Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A . 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res. 2010; 70(8):3052-61. DOI: 10.1158/0008-5472.CAN-09-3690. View

13.

van Geffen C, Deissler A, Beer-Hammer S, Nurnberg B, Handgretinger R, Renz H . Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4. Front Immunol. 2021; 12:695933. PMC: 8311661. DOI: 10.3389/fimmu.2021.695933. View

14.

Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini P, Zamboni P . Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood. 2000; 96(12):3838-46. PMC: 2734459. View

15.

Zhang J, Hodges A, Chen S, Pan P . Myeloid-derived suppressor cells as cellular immunotherapy in transplantation and autoimmune diseases. Cell Immunol. 2021; 362:104300. PMC: 8019491. DOI: 10.1016/j.cellimm.2021.104300. View

16.

Deshane J, Zmijewski J, Luther R, Gaggar A, Deshane R, Lai J . Free radical-producing myeloid-derived regulatory cells: potent activators and suppressors of lung inflammation and airway hyperresponsiveness. Mucosal Immunol. 2011; 4(5):503-18. PMC: 3694614. DOI: 10.1038/mi.2011.16. View

17.

van Geffen C, Heiss C, Deissler A, Kolahian S . Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation. Front Immunol. 2022; 13:933847. PMC: 9468781. DOI: 10.3389/fimmu.2022.933847. View

18.

De Cicco P, Ercolano G, Ianaro A . The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion. Front Immunol. 2020; 11:1680. PMC: 7406792. DOI: 10.3389/fimmu.2020.01680. View

19.

Hansbro P, Kim R, Starkey M, Donovan C, Dua K, Mayall J . Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma. Immunol Rev. 2017; 278(1):41-62. DOI: 10.1111/imr.12543. View

20.

Zhang M, Yuan Y, Ao S . Advances in the study of myeloid-derived suppressor cells in infectious lung diseases. Front Immunol. 2023; 14:1125737. PMC: 10090681. DOI: 10.3389/fimmu.2023.1125737. View