title: Preserved dendritic cell HLA-DR expression and reduced regulatory T cell activation in asymptomatic Plasmodium falciparum and P. vivax infection.
abstract: Clinical illness with Plasmodium falciparum or Plasmodium vivax compromises the function of dendritic cells (DC) and expands regulatory T (Treg) cells. Individuals with asymptomatic parasitemia have clinical immunity, restricting parasite expansion and preventing clinical disease. The role of DC and Treg cells during asymptomatic Plasmodium infection is unclear. During a cross-sectional household survey in Papua, Indonesia, we examined the number and activation of blood plasmacytoid DC (pDC), CD141(+), and CD1c(+) myeloid DC (mDC) subsets and Treg cells using flow cytometry in 168 afebrile children (of whom 15 had P. falciparum and 36 had P. vivax infections) and 162 afebrile adults (of whom 20 had P. falciparum and 20 had P. vivax infections), alongside samples from 16 patients hospitalized with uncomplicated malaria. Unlike DC from malaria patients, DC from children and adults with asymptomatic, microscopy-positive P. vivax or P. falciparum infection increased or retained HLA-DR expression. Treg cells in asymptomatic adults and children exhibited reduced activation, suggesting increased immune responsiveness. The pDC and mDC subsets varied according to clinical immunity (asymptomatic or symptomatic Plasmodium infection) and, in asymptomatic infection, according to host age and parasite species. In conclusion, active control of asymptomatic infection was associated with and likely contingent upon functional DC and reduced Treg cell activation.
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Kho
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Jutta
authors.initials: J
authors.lastname: Marfurt
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Rintis
authors.initials: R
authors.lastname: Noviyanti
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kusuma
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Piera
authors.affiliation: Timika Malaria Research Programme, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia.
authors.forename: Faustina H
authors.initials: FH
authors.lastname: Burdam
authors.affiliation: Timika Malaria Research Programme, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia Rumah Sakit Umum Daerah Kabupaten Mimika, Timika, Papua, Indonesia.
authors.forename: Enny
authors.initials: E
authors.lastname: Kenangalem
authors.affiliation: Timika Malaria Research Programme, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lampah
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Engwerda
authors.affiliation: Timika Malaria Research Programme, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia Rumah Sakit Umum Daerah Kabupaten Mimika, Timika, Papua, Indonesia Department of Paediatrics, University of Gadjah Mada, Yogyakarta, Indonesia.
authors.forename: Jeanne R
authors.initials: JR
authors.lastname: Poespoprodjo
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Minigo
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia Tonia.Woodberry@menzies.edu.au.
authors.forename: Tonia
authors.initials: T
authors.lastname: Woodberry
mesh_terms: D000293:Adolescent; D000328:Adult; D058070:Asymptomatic Diseases; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007214:Indonesia; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D016780:Malaria, Vivax / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology*; D010966:Plasmodium vivax / Q000276:immunology / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D006684:HLA-DR Antigens