Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus

Zhaohui Qian, Emily A. Travanty, Lauren Oko, Karen Edeen, Andrew Berglund, Jieru Wang, Yoko Ito, Kathryn V. Holmes, Robert J. Mason

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Severe acute respiratory syndrome (SARS)-coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the majorcell types tobeinfectedis the alveolar type II cell. However,the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an air- liquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon-β and interferon-λ (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme-2, the SARS-CoV receptor, in type II cells fromdifferent donors. In conclusion, the cultivation of alveolar type II cells at an air-liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.

Original languageEnglish
Pages (from-to)742-748
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume48
Issue number6
DOIs
Publication statusPublished - 2013 Jun

Fingerprint

Alveolar Epithelial Cells
Severe Acute Respiratory Syndrome
Coronavirus
Innate Immunity
Interferons
Chemokines
Cytokines
Viral Antigens
Virion
Liquids
Air
Viruses
Viral Pneumonia
Coronavirus Infections
RNA
RNA Viruses
Exocytosis
Secretory Vesicles
Messenger RNA
Infection

Keywords

  • Air-liquid interface cultures
  • Cytokine responses to SARS coronavirus
  • Lung cell differentiation
  • Lung innate immune response

ASJC Scopus subject areas

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

Cite this

Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. / Qian, Zhaohui; Travanty, Emily A.; Oko, Lauren; Edeen, Karen; Berglund, Andrew; Wang, Jieru; Ito, Yoko; Holmes, Kathryn V.; Mason, Robert J.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 48, No. 6, 06.2013, p. 742-748.

Research output: Contribution to journalArticle

Qian, Zhaohui ; Travanty, Emily A. ; Oko, Lauren ; Edeen, Karen ; Berglund, Andrew ; Wang, Jieru ; Ito, Yoko ; Holmes, Kathryn V. ; Mason, Robert J. / Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. In: American Journal of Respiratory Cell and Molecular Biology. 2013 ; Vol. 48, No. 6. pp. 742-748.
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