title: A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity.
abstract: 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.
authors: Department of Immunology, Armed Forces Research Institute of Medical Sciences, Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
authors: Sathit
authors: S
authors: Pichyangkul
authors: Timothy P
authors: TP
authors: Endy
authors: Siripen
authors: S
authors: Kalayanarooj
authors: Ananda
authors: A
authors: Nisalak
authors: Kosol
authors: K
authors: Yongvanitchit
authors: Sharone
authors: S
authors: Green
authors: Alan L
authors: AL
authors: Rothman
authors: Francis A
authors: FA
authors: Ennis
authors: Daniel H
authors: DH
authors: Libraty
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003715:Dengue / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007223:Infant; D007370:Interferon Type I / Q000627:therapeutic use; D016898:Interferon-alpha / Q000378:metabolism; D007958:Leukocyte Count; D008253:Macaca mulatta; D008297:Male; D023461:Myeloid Progenitor Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011446:Prospective Studies; D011994:Recombinant Proteins; D019595:Severe Dengue / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins