Prior exposure to inhaled allergen enhances anti-viral immunity and T cell priming by dendritic cells

PLoS One. 2018 Jan 2;13(1):e0190063. doi: 10.1371/journal.pone.0190063. eCollection 2018.

Abstract

Influenza and asthma are two of the major public health concerns in the world today. During the 2009 influenza pandemic asthma was found to be the commonest comorbid illness of patients admitted to hospital. Unexpectedly, it was also observed that asthmatic patients admitted to hospital with influenza infection were less likely to die or require admission to intensive care compared with non-asthmatics. Using an in vivo model of asthma and influenza infection we demonstrate that prior exposure to Blomia tropicalis extract (BTE) leads to an altered immune response to influenza infection, comprised of less severe weight loss and faster recovery following infection. This protection was associated with significant increases in T cell numbers in the lungs of BTE sensitised and infected mice, as well as increased IFN-γ production from these cells. In addition, elevated numbers of CD11b+ dendritic cells (DCs) were found in the lung draining lymph nodes following infection of BTE sensitised mice compared to infected PBS treated mice. These CD11b+ DCs appeared to be better at priming CD8 specific T cells both in vivo and ex vivo, a function not normally attributed to CD11b+ DCs. We propose that this alteration in cross-presentation and more efficient T cell priming seen in BTE sensitised mice, led to the earlier increase in T cells in the lungs and subsequently faster clearance of the virus and reduced influenza induced pathology. We believe this data provides a novel mechanism that explains why asthmatic patients may present with less severe disease when infected with influenza.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / administration & dosage*
  • Animals
  • Asthma / complications
  • Asthma / immunology*
  • Bronchoalveolar Lavage Fluid
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Influenza A virus / immunology*
  • Inhalation Exposure
  • Interferon-gamma / biosynthesis
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / complications
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / virology
  • Plant Extracts / pharmacology
  • T-Lymphocytes / immunology*
  • Viral Load

Substances

  • Allergens
  • Plant Extracts
  • Interferon-gamma

Grants and funding

This work was supported by National Medical Research Council of Singapore Grant No. NMRC/1262/2010, http://www.nmrc.gov.sg and the National Research Foundation of Singapore Grant No. NRF370062-HUJ-NUS, https://www.nrf.gov.sg. All funding was awarded to DMK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.