Myeloid-derived suppressor cells in influenza virus-induced asthma exacerbation

Front Immunol. 2024 Apr 17:15:1342497. doi: 10.3389/fimmu.2024.1342497. eCollection 2024.

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.

Keywords: asthma; asthma exacerbation; inflammation; influenza virus; myeloid-derived suppressor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma* / immunology
  • Cytokines* / metabolism
  • Disease Models, Animal*
  • Disease Progression
  • Female
  • Influenza A Virus, H1N1 Subtype* / immunology
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C*
  • Myeloid-Derived Suppressor Cells* / immunology
  • Orthomyxoviridae Infections* / immunology
  • Pyroglyphidae / immunology
  • Th2 Cells / immunology

Substances

  • Cytokines

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Universities Giessen Marburg Lung Center (UGMLC) and the German Center for Lung Disease (DZL German Lung Center, no. 82DZL005B2), the Foundation for Pathobiochemistry and Molecular Diagnostics grant, fortüne program of the University of Tuebingen (# 2458-0-0, # 2606-0-0) and the German Research Foundation (Deutsche Forschungsgemeinschaft: DFG Grant No. 519089268) for SK. We acknowledge support from the Open Access Publishing Funds of the University of Tübingen and the Philipps University Marburg.