Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells.
Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV-infected DCs. The SARS-CoV-infected DCs showed low expression of antiviral cytokines (interferon alpha [IFN-alpha], IFN-beta, IFN-gamma, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.
Law
Helen K W
HK
Department of Paediatrics and Adolescent Medicine, Hong Kong Jockey Club Clinical Research Centre, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Cheung
Chung Yan
CY
Ng
Hoi Yee
HY
Sia
Sin Fun
SF
Chan
Yuk On
YO
Luk
Winsie
W
Nicholls
John M
JM
Peiris
J S Malik
JS
Lau
Yu Lung
YL
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002469:Cell Separation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology*; D004789:Enzyme Activation; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007249:Inflammation; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology*; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D021122:Protein Subunits; D012367:RNA, Viral; D018664:Interleukin-12; D012313:RNA; D016899:Interferon-beta; D007371:Interferon-gamma; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases