Modulation of airway epithelial antiviral immunity by fungal exposure

Lingxiang Zhu, Boram Lee, Fangkun Zhao, Xu Zhou, Vanessa Chin, Serena C. Ling, Yin Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Multiple pathogens, such as bacteria, fungi, and viruses, have been frequently found in asthmatic airways and are associated with the pathogenesis and exacerbation of asthma. Among these pathogens, Alternaria alternata (Alt), a universally present fungus, and human rhinovirus have been extensively studied. However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA). Alt treatment was found to significantly enhance the production of proinflammatory cytokines (e.g., IL-6 and IL-8) induced by virus infection or dsRNA treatment. In contrast to this synergistic effect, Alt significantly repressed type I and type III IFN production, and this impairment led to elevated viral replication. Mechanistic studies suggested the positive role of NF-κB and mitogen-activated protein kinase pathways in the synergism and the attenuation of the TBK1-IRF3 pathway in the inhibition of IFN production. These opposite effects are caused by separate fungal components. Protease-dependent and -independent mechanisms appear to be involved. Thus, Alt exposure alters the airway epithelial immunity to viral infection by shifting toward more inflammatory but less antiviral responses.

Original languageEnglish (US)
Pages (from-to)1136-1143
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume50
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Viruses
Antiviral Agents
Immunity
Double-Stranded RNA
Modulation
Virus Diseases
Pathogens
Fungi
Fungal Structures
Rhinovirus
Alternaria
Mitogen-Activated Protein Kinases
Interleukin-8
Interleukin-6
Peptide Hydrolases
Asthma
Cytokines
Bacteria

Keywords

  • Alternaria
  • Antiviral
  • Epithelium
  • Rhinovirus
  • Toll-like receptor 3

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Modulation of airway epithelial antiviral immunity by fungal exposure. / Zhu, Lingxiang; Lee, Boram; Zhao, Fangkun; Zhou, Xu; Chin, Vanessa; Ling, Serena C.; Chen, Yin.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 50, No. 6, 2014, p. 1136-1143.

Research output: Contribution to journalArticle

Zhu, Lingxiang ; Lee, Boram ; Zhao, Fangkun ; Zhou, Xu ; Chin, Vanessa ; Ling, Serena C. ; Chen, Yin. / Modulation of airway epithelial antiviral immunity by fungal exposure. In: American Journal of Respiratory Cell and Molecular Biology. 2014 ; Vol. 50, No. 6. pp. 1136-1143.
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