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Journal of Virology, April 2009, p. 3039-3048, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.01792-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Severe Acute Respiratory Syndrome (SARS) Coronavirus-Induced Lung Epithelial Cytokines Exacerbate SARS Pathogenesis by Modulating Intrinsic Functions of Monocyte-Derived Macrophages and Dendritic Cells{triangledown}

Tomoki Yoshikawa,1 Terence Hill,1 Kui Li,1 Clarence J. Peters,1,2,3 and Chien-Te K. Tseng1,3*

Departments of Microbiology and Immunology,1 Pathology,2 Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas 775553

Received 26 August 2008/ Accepted 5 November 2008

Severe acute respiratory syndrome (SARS), which is caused by a novel coronavirus (CoV), is a highly communicable disease with the lungs as the major pathological target. Although SARS likely stems from overexuberant host inflammatory responses, the exact mechanism leading to the detrimental outcome in patients remains unknown. Pulmonary macrophages (M{phi}), airway epithelium, and dendritic cells (DC) are key cellular elements of the host innate defenses against respiratory infections. While pulmonary M{phi} are situated at the luminal epithelial surface, DC reside abundantly underneath the epithelium. Such strategic locations of these cells within the airways make it relevant to investigate their likely impact on SARS pathogenesis subsequent to their interaction with infected lung epithelial cells. To study this, we established highly polarized human lung epithelial Calu-3 cells by using the Transwell culture system. Here we report that supernatants harvested from the apical and basolateral domains of infected Calu-3 cells are potent in modulating the intrinsic functions of M{phi} and DC, respectively. They prompted the production of cytokines by both M{phi} and DC and selectively induced CD40 and CD86 expression only on DC. However, they compromised the abilities of the DC and M{phi} in priming naïve T cells and phagocytosis, respectively. We also identified interleukin-6 (IL-6) and IL-8 as key SARS-CoV-induced epithelial cytokines capable of inhibiting the T-cell-priming ability of DC. Taken together, our results provide insights into the molecular and cellular bases of the host antiviral innate immunity within the lungs that eventually lead to an exacerbated inflammatory cascades and severe tissue damage in SARS patients.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, G-150 Keiller Building, Galveston, TX 77555-0609. Phone: (409)747-0789. Fax: (409)747-0762. E-mail: sktseng{at}utmb.edu

{triangledown} Published ahead of print on 12 November 2008.

Journal of Virology, April 2009, p. 3039-3048, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.01792-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Miura, T. A., Holmes, K. V. (2009). Host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells. J. Leukoc. Biol. 86: 1145-1151 [Abstract] [Full Text]  


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