Innate immune response of human alveolar type II cells infected with SARS-coronavirus.

Qian Z, Travanty EA, Oko L, Edeen K, Berglund A, Wang J, Ito Y, Holmes KV, Mason R.

Citation

Qian Z, Travanty EA, Oko L, Edeen K, Berglund A, Wang J, Ito Y, Holmes KV, Mason R. (2013) Innate immune response of human alveolar type II cells infected with SARS-coronavirus. American Journal of Respiratory Cell and Molecular Biology

Abstract

Rationale: SARS-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. Objectives: The objectives were to develop a culture system permissive for SARS-CoV infection in primary human type II cells and to define their innate immune response. Methods: Culturing primary human alveolar type II cells at an air/liquid interface (ALI) improved their differentiation and greatly increased their susceptibility to infection so that we were able to define their primary interferon and chemokine responses. Measurements and Main Results: Viral antigens were detected in the cytoplasm of the infected type II cells, electron micrographs demonstrated vesicles filled with virions, virus specific RNA levels increased with time, and infectious virus was released from the apical surface of the polarized type II cells. There was a marked increase in the mRNA levels of interferon beta and lambda (IL-29) and a large number of proinflammatory cytokines and chemokines. A surprising finding in this study was the variability of the expression of angiotension converting enzyme 2, the SARS-CoV receptor, in type II cells from different donors. Conclusions: 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 their innate immune response.