Please use this identifier to cite or link to this item: https://hdl.handle.net/10137/5380
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 JR
Minigo G
Burel J
Tipping PE
Piera KA
Amante FH
Engwerda CR
Good MF
Doolan DL
Anstey NM
McCarthy JS
Woodberry T
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.
Click to open PubMed article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed//26902728
Journal title: Infection and immunity
Publication Date: 2016
Type: Journal Article
URI: https://hdl.handle.net/10137/5380
DOI: 10.1128/IAI.01522-15
Appears in Collections:(a) NT Health Research Collection

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