title: Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria.
abstract: Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes. Circulating DCs are particularly important, as they shape immune responses in vivo and reflect the functional status of other subpopulations. We performed cross-sectional and longitudinal assessments of the frequency, phenotype, and function of circulating DC in 67 Papuan adults during acute uncomplicated P. falciparum, P. vivax, and convalescent P. falciparum infections. We demonstrate that malaria patients display a significant reduction in circulating DC numbers and the concurrent accumulation of immature cells. Such alteration is associated with marked levels of spontaneous apoptosis and impairment in the ability of DC to mature, capture, and present antigens to T cells. Interestingly, sustained levels of plasma IL-10 were observed in patients with acute infection and were implicated in the induction of DC apoptosis. DC apoptosis was reversed upon IL-10 blockade, and DC function recovered when IL-10 levels returned to baseline by convalescence. Our data provide key information on the mechanisms behind DC suppression during malaria and will assist in developing strategies to better harness DC's immunotherapeutic potential.
authors.affiliation: Queensland Institute of Medical Research, Brisbane QLD 4006, Australia. Michael.good@griffith.edu.au
authors.forename: Alberto
authors.initials: A
authors.lastname: Pinzon-Charry
authors.forename: Tonia
authors.initials: T
authors.lastname: Woodberry
authors.forename: Vivian
authors.initials: V
authors.lastname: Kienzle
authors.forename: Virginia
authors.initials: V
authors.lastname: McPhun
authors.forename: Gabriela
authors.initials: G
authors.lastname: Minigo
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lampah
authors.forename: Enny
authors.initials: E
authors.lastname: Kenangalem
authors.forename: Christian
authors.initials: C
authors.lastname: Engwerda
authors.forename: J Alejandro
authors.initials: JA
authors.lastname: López
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D000962:Antimalarials / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001772:Blood Cell Count; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000097:blood / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology; D016780:Malaria, Vivax / Q000097:blood* / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology; D008297:Male; D010641:Phenotype; D055815:Young Adult
chemical_list: D000941:Antigens; D000962:Antimalarials; D016207:Cytokines; D016753:Interleukin-10