Innate Immune Response of Human Alveolar Type II Cells Infected with Severe Acute Respiratory Syndrome–Coronavirus
Autor: | Andrew Berglund, Emily A. Travanty, Yoko Ito, Kathryn V. Holmes, Robert J. Mason, Zhaohui Qian, Karen E. Edeen, Lauren M. Oko, Jieru Wang |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Pulmonary and Respiratory Medicine
Chemokine Cytoplasm Time Factors Cellular differentiation viruses Clinical Biochemistry Primary Cell Culture Respiratory Mucosa Biology Peptidyl-Dipeptidase A Severe Acute Respiratory Syndrome Antigen Interferon Immunity medicine Humans RNA Messenger Diffuse alveolar damage Molecular Biology Antigens Viral Virus Release Innate immune system Interleukins Cell Differentiation Epithelial Cells Cell Biology Articles Interferon-beta Immunity Innate Pulmonary Alveoli Severe acute respiratory syndrome-related coronavirus Immunology biology.protein Lung cell differentiation Receptors Virus Angiotensin-Converting Enzyme 2 Interferons medicine.drug |
Zdroj: | American Journal of Respiratory Cell and Molecular Biology |
Popis: | 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 major cell types to be infected is 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 from different 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. |
Databáze: | OpenAIRE |
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