Loughland JR; Minigo G; Burel J; Tipping PE; Piera KA; Amante FH; Engwerda CR; Good MF; Doolan DL; Anstey NM; McCarthy JS; Woodberry T

Author(s)

Loughland JR

Minigo G

Burel J

Tipping PE

Piera KA

Amante FH

Engwerda CR

Good MF

Doolan DL

Anstey NM

McCarthy JS

Woodberry T

Publication Date

2016

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.

Citation

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

Pubmed ID

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

Link

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

MESH subject

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

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.

Type of document

Journal Article

Entity Type

Publication

Author(s)	Loughland JR Minigo G Burel J Tipping PE Piera KA Amante FH Engwerda CR Good MF Doolan DL Anstey NM McCarthy JS Woodberry T
Publication Date	2016
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.
Citation	Infection and immunity 2016; 84(5): 1403-1412
Pubmed ID	https://pubmed.ncbi.nlm.nih.gov/26902728/?otool=iaurydwlib
Link	https://hdl.handle.net/10137/5380
MESH subject	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
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.
Type of document	Journal Article
Entity Type	Publication

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

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