A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity
Authors
Pichyangkul, SathitEndy, Timothy P.
Kalayanarooj, Siripen
Nisalak, Ananda
Yongvanitchit, Kosol
Green, Sharone
Rothman, Alan L.
Ennis, Francis A.
Libraty, Daniel H.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyCenter for Infectious Disease and Vaccine Research
Document Type
Journal ArticlePublication Date
2003-11-15Keywords
ImmunityImmunology and Infectious Disease
Immunology of Infectious Disease
Infectious Disease
Metadata
Show full item recordAbstract
At least two distinct human dendritic cell (DC) subsets are produced in the bone marrow and circulate in the peripheral blood-precursor myeloid DCs (pre-mDCs) and plasmacytoid DCs (PDCs). Both lineages of DCs are instrumental in antiviral innate immunity and shaping Th1 adaptive immune responses. PDCs are the most potent IFN-alpha-producing cells to viral pathogens. Dengue, an acute flavivirus disease, provides a model to study DC responses to a self-limited human viral infection. We analyzed circulating DC subsets in a prospective study of children with dengue across a broad range of illness severities: healthy controls; mild, nondengue, presumed viral infections; moderately ill dengue fever; and, the most severe form of illness, dengue hemorrhagic fever. We also examined PDC responses in monkeys with asymptomatic dengue viremia and to dengue virus exposure in vitro. The absolute number and frequency of circulating pre-mDCs early in acute viral illness decreased as illness severity increased. Depressed pre-mDC blood levels appeared to be part of the typical innate immune response to acute viral infection. The frequency of circulating PDCs trended upward and the absolute number of circulating PDCs remained stable early in moderately ill children with dengue fever, mild other, nondengue, febrile illness, and monkeys with asymptomatic dengue viremia. However, there was an early decrease in circulating PDC levels in children who subsequently developed dengue hemorrhagic fever. A blunted blood PDC response to dengue virus infection was associated with higher viremia levels, and was part of an altered innate immune response and pathogenetic cascade leading to severe disease.Source
J Immunol. 2003 Nov 15;171(10):5571-8. doi: 10.4049/jimmunol.171.10.5571DOI
10.4049/jimmunol.171.10.5571Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35057PubMed ID
14607965Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.171.10.5571