title: Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus.
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 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.
authors: Department of Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
authors: Zhaohui
authors: Z
authors: Qian
authors: Emily A
authors: EA
authors: Travanty
authors: Lauren
authors: L
authors: Oko
authors: Karen
authors: K
authors: Edeen
authors: Andrew
authors: A
authors: Berglund
authors: Jieru
authors: J
authors: Wang
authors: Yoko
authors: Y
authors: Ito
authors: Kathryn V
authors: KV
authors: Holmes
authors: Robert J
authors: RJ
authors: Mason
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D003593:Cytoplasm / Q000276:immunology / Q000648:ultrastructure / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000276:immunology / Q000378:metabolism; D061251:Primary Cell Culture; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000821:virology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology*; D013997:Time Factors; D057074:Virus Release; D000095022:Interferon Lambda
chemical_list: D000085962:Angiotensin-Converting Enzyme 2; D000956:Antigens, Viral; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D007703:Peptidyl-Dipeptidase A; D012333:RNA, Messenger; D011991:Receptors, Virus; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C000705307:ACE2 protein, human