Loughland JR

Minigo G

Burel J

Tipping PE

Piera KA

Amante FH

Engwerda CR

Good MF

Doolan DL

Anstey NM

McCarthy JS

Woodberry T

2016

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.

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..

Infection and immunity 2016; 84(5): 1403-1412

https://pubmed.ncbi.nlm.nih.gov/26902728/?otool=iaurydwlib

https://hdl.handle.net/10137/5380

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

Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection.

Journal Article

Publication