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

Tomoki Yoshikawa, Terence Hill, Kui Li, Clarence J. Peters, Chien-Te Tseng

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)3039-3048
Number of pages10
JournalJournal of Virology
Volume83
Issue number7
DOIs
StatePublished - Apr 2009

Fingerprint

Severe Acute Respiratory Syndrome
Coronavirus
dendritic cells
monocytes
Dendritic Cells
macrophages
cytokines
pathogenesis
lungs
Macrophages
Cytokines
Lung
epithelium
Epithelium
T-lymphocytes
T-Lymphocytes
Cytophagocytosis
Coronavirinae
interleukin-8
Alveolar Macrophages

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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, Tomoki; Hill, Terence; Li, Kui; Peters, Clarence J.; Tseng, Chien-Te.

In: Journal of Virology, Vol. 83, No. 7, 04.2009, p. 3039-3048.

Research output: Contribution to journalArticle

@article{348877e3126c48a3b40e751c8334f00d,
title = "Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells",
abstract = "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 (MΦ), airway epithelium, and dendritic cells (DC) are key cellular elements of the host innate defenses against respiratory infections. While pulmonary MΦ 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 MΦ and DC, respectively. They prompted the production of cytokines by both MΦ and DC and selectively induced CD40 and CD86 expression only on DC. However, they compromised the abilities of the DC and MΦ in priming naive 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.",
author = "Tomoki Yoshikawa and Terence Hill and Kui Li and Peters, {Clarence J.} and Chien-Te Tseng",
year = "2009",
month = "4",
doi = "10.1128/JVI.01792-08",
language = "English (US)",
volume = "83",
pages = "3039--3048",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells

AU - Yoshikawa, Tomoki

AU - Hill, Terence

AU - Li, Kui

AU - Peters, Clarence J.

AU - Tseng, Chien-Te

PY - 2009/4

Y1 - 2009/4

N2 - 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 (MΦ), airway epithelium, and dendritic cells (DC) are key cellular elements of the host innate defenses against respiratory infections. While pulmonary MΦ 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 MΦ and DC, respectively. They prompted the production of cytokines by both MΦ and DC and selectively induced CD40 and CD86 expression only on DC. However, they compromised the abilities of the DC and MΦ in priming naive 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.

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

UR - http://www.scopus.com/inward/record.url?scp=63149161765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63149161765&partnerID=8YFLogxK

U2 - 10.1128/JVI.01792-08

DO - 10.1128/JVI.01792-08

M3 - Article

C2 - 19004938

AN - SCOPUS:63149161765

VL - 83

SP - 3039

EP - 3048

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 7

ER -