Please use this identifier to cite or link to this item: http://docs.prosentient.com.au/prosentientjspui/handle/1/10412
Title: Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection.
Authors: Loughland, Jessica R
Minigo, Gabriela
Burel, Julie
Tipping, Peta E
Piera, Kim A
Amante, Fiona H
Engwerda, Christian R
Good, Michael F
Doolan, Denise L
Anstey, Nicholas M
McCarthy, James S
Woodberry, Tonia
Affiliation: Menzies School of Health Research, Darwin, Australia, and Charles Darwin University, Darwin, Australia jessica.loughland@menzies.edu.au..
Menzies School of Health Research, Darwin, Australia, and Charles Darwin University, Darwin, Australia..
QIMR Berghofer Medical Research Institute and University of Queensland, Brisbane, Australia..
Menzies School of Health Research, Darwin, Australia, and Charles Darwin University, Darwin, Australia..
Menzies School of Health Research, Darwin, Australia, and Charles Darwin University, Darwin, Australia..
QIMR Berghofer Medical Research Institute and University of Queensland, Brisbane, Australia..
QIMR Berghofer Medical Research Institute and University of Queensland, Brisbane, Australia..
Griffith University, Gold Coast, Queensland, Australia..
QIMR Berghofer Medical Research Institute and University of Queensland, Brisbane, Australia..
Menzies School of Health Research, Darwin, Australia, and Charles Darwin University, Darwin, Australia.. Royal Darwin Hospital, Darwin, Australia..
QIMR Berghofer Medical Research Institute and University of Queensland, Brisbane, Australia..
Menzies School of Health Research, Darwin, Australia, and Charles Darwin University, Darwin, Australia..
Issue Date: 2016
Citation: Infection and immunity 2016; 84(5): 1403-1412
Abstract: Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c(+) mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c(+) mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs). After either dose, CD1c(+) mDCs significantly reduced HLA-DR expression in prepatent infections. Circulating CD1c(+) mDCs did not upregulate HLA-DR after pRBC or TLR ligand stimulation and exhibited reduced CD86 expression. At peak parasitemia, CD1c(+) mDCs produced significantly more tumor necrosis factor (TNF), whereas interleukin-12 (IL-12) production was unchanged. Interestingly, only the 1,800-pRBC dose caused a reduction in the circulating CD1c(+) mDC count with evidence of apoptosis. The 1,800-pRBC dose produced no change in T cell IFN-γ or IL-2 production at peak parasitemia or at 3 weeks posttreatment. Overall, CD1c(+) mDCs are compromised by P. falciparum exposure, with impaired HLA-DR and CD86 expression, and have an increased capacity for TNF but not IL-12 production. A first prepatent P. falciparum infection is sufficient to modulate CD1c(+) mDC responsiveness, likely contributing to hampered effector T cell cytokine responses and assisting parasite immune evasion.
URI: http://docs.prosentient.com.au/prosentientjspui/handle/1/10412
DOI: 10.1128/IAI.01522-15
Type: Journal Article
Subjects: Adult
Antigens, CD1
B7-2 Antigen
Cohort Studies
Dendritic Cells
Female
Glycoproteins
HLA-DR Antigens
Healthy Volunteers
Humans
Malaria, Falciparum
Male
Plasmodium falciparum
Tumor Necrosis Factor-alpha
Young Adult
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