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			PubMed Journals: J Virol

  Source:		PMID: 19004938
  Download:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655569/pdf/1792-08.pdf

    		J Virol. 2009 Apr;83(7):3039-48. doi:
     		10.1128/JVI.01792-08. Epub 2008 Nov 12.

			Severe acute respiratory syndrome (SARS)
			coronavirus-induced lung epithelial cytokines
			exacerbate SARS pathogenesis by modulating
			intrinsic functions of monocyte-derived
			macrophages and dendritic cells.

			Yoshikawa T(1), Hill T, Li K, Peters CJ,
			Tseng CT.

			Author Information
			(1) Department of Microbiology and Immunology,
			University of Texas Medical Branch, Galveston,
			Texas 77555-0609, USA.

			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 (Mphi),
			airway epithelium, and dendritic cells (DC)
			are key cellular elements of the host innate
			defenses against respiratory infections.
			While pulmonary Mphi 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 Mphi and DC, respectively.
			They prompted the production of cytokines
			by both Mphi and DC and selectively induced
			CD40 and CD86 expression only on DC. However,
			they compromised the abilities of the DC
			and Mphi 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.

			DOI: 10.1128/JVI.01792-08 PMCID: PMC2655569
			PMID: 19004938 [Indexed for MEDLINE]

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