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Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection.
PLoS One. 2010 Jan 15; 5(1):e8729.Plos

Abstract

Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarray-based functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NF)kappaB, activator protein (AP)-1, and interferon regulatory factor (IRF)-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i.), resulting in the activation of many antiviral genes, including interferon (IFN)-beta, -lambdas, inflammatory mediators, and many IFN-stimulated genes (ISGs). We also showed, for the first time, that IFN-beta and IFN-lambdas were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS.

Authors+Show Affiliations

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20090954

Citation

Yoshikawa, Tomoki, et al. "Dynamic Innate Immune Responses of Human Bronchial Epithelial Cells to Severe Acute Respiratory Syndrome-associated Coronavirus Infection." PloS One, vol. 5, no. 1, 2010, pp. e8729.
Yoshikawa T, Hill TE, Yoshikawa N, et al. Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection. PLoS ONE. 2010;5(1):e8729.
Yoshikawa, T., Hill, T. E., Yoshikawa, N., Popov, V. L., Galindo, C. L., Garner, H. R., Peters, C. J., & Tseng, C. T. (2010). Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection. PloS One, 5(1), e8729. https://doi.org/10.1371/journal.pone.0008729
Yoshikawa T, et al. Dynamic Innate Immune Responses of Human Bronchial Epithelial Cells to Severe Acute Respiratory Syndrome-associated Coronavirus Infection. PLoS ONE. 2010 Jan 15;5(1):e8729. PubMed PMID: 20090954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection. AU - Yoshikawa,Tomoki, AU - Hill,Terence E, AU - Yoshikawa,Naoko, AU - Popov,Vsevolod L, AU - Galindo,Cristi L, AU - Garner,Harold R, AU - Peters,C J, AU - Tseng,Chien-Te Kent, Y1 - 2010/01/15/ PY - 2009/09/12/received PY - 2009/12/18/accepted PY - 2010/1/22/entrez PY - 2010/1/22/pubmed PY - 2010/5/21/medline SP - e8729 EP - e8729 JF - PloS one JO - PLoS ONE VL - 5 IS - 1 N2 - Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarray-based functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NF)kappaB, activator protein (AP)-1, and interferon regulatory factor (IRF)-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i.), resulting in the activation of many antiviral genes, including interferon (IFN)-beta, -lambdas, inflammatory mediators, and many IFN-stimulated genes (ISGs). We also showed, for the first time, that IFN-beta and IFN-lambdas were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/20090954/Dynamic_innate_immune_responses_of_human_bronchial_epithelial_cells_to_severe_acute_respiratory_syndrome_associated_coronavirus_infection_ L2 - http://dx.plos.org/10.1371/journal.pone.0008729 DB - PRIME DP - Unbound Medicine ER -