PubMed Journals: J Virol
Source: PMID: 19004938
⇦ ⇨ 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,
(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]