Profoundly reduced CD1c+ myeloid dendritic cell HLA-DR and CD86 expression and increased tumor necrosis factor production in experimental human bloodstage malaria infection

Jessica Rita Loughland, Gabriela Minigo, J Burel, PE Tipping, Kim Piera, Fiona Amante, Christian Engwerda, M GOOD, D DOOLAN, Nicholas Anstey, James McCarthy, Tonia Woodberry

Research output: Contribution to journalArticleResearchpeer-review

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-? 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. � 2016, American Society for Microbiology. All Rights Reserved.
Original languageEnglish
Pages (from-to)1403-1412
Number of pages10
JournalInfection and Immunity
Volume84
Issue number5
DOIs
Publication statusPublished - 2016

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HLA-DR Antigens
Myeloid Cells
Dendritic Cells
Malaria
Parasites
Tumor Necrosis Factor-alpha
Plasmodium falciparum
Erythrocytes
Infection
Parasitemia
Toll-Like Receptors
Interleukin-12
Cytokines
T-Lymphocytes
Immune Evasion
Adaptive Immunity
Microbiology
Interleukin-2
Immune System
Healthy Volunteers

Cite this

Loughland, Jessica Rita ; Minigo, Gabriela ; Burel, J ; Tipping, PE ; Piera, Kim ; Amante, Fiona ; Engwerda, Christian ; GOOD, M ; DOOLAN, D ; Anstey, Nicholas ; McCarthy, James ; Woodberry, Tonia. / Profoundly reduced CD1c+ myeloid dendritic cell HLA-DR and CD86 expression and increased tumor necrosis factor production in experimental human bloodstage malaria infection. In: Infection and Immunity. 2016 ; Vol. 84, No. 5. pp. 1403-1412.
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title = "Profoundly reduced CD1c+ myeloid dendritic cell HLA-DR and CD86 expression and increased tumor necrosis factor production in experimental human bloodstage malaria infection",
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-? 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. � 2016, American Society for Microbiology. All Rights Reserved.",
author = "Loughland, {Jessica Rita} and Gabriela Minigo and J Burel and PE Tipping and Kim Piera and Fiona Amante and Christian Engwerda and M GOOD and D DOOLAN and Nicholas Anstey and James McCarthy and Tonia Woodberry",
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Profoundly reduced CD1c+ myeloid dendritic cell HLA-DR and CD86 expression and increased tumor necrosis factor production in experimental human bloodstage malaria infection. / Loughland, Jessica Rita; Minigo, Gabriela; Burel, J; Tipping, PE; Piera, Kim; Amante, Fiona; Engwerda, Christian; GOOD, M; DOOLAN, D; Anstey, Nicholas; McCarthy, James; Woodberry, Tonia.

In: Infection and Immunity, Vol. 84, No. 5, 2016, p. 1403-1412.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Profoundly reduced CD1c+ myeloid dendritic cell HLA-DR and CD86 expression and increased tumor necrosis factor production in experimental human bloodstage malaria infection

AU - Loughland, Jessica Rita

AU - Minigo, Gabriela

AU - Burel, J

AU - Tipping, PE

AU - Piera, Kim

AU - Amante, Fiona

AU - Engwerda, Christian

AU - GOOD, M

AU - DOOLAN, D

AU - Anstey, Nicholas

AU - McCarthy, James

AU - Woodberry, Tonia

PY - 2016

Y1 - 2016

N2 - 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-? 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. � 2016, American Society for Microbiology. All Rights Reserved.

AB - 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-? 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. � 2016, American Society for Microbiology. All Rights Reserved.

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U2 - 10.1128/IAI.01522-15

DO - 10.1128/IAI.01522-15

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SP - 1403

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JF - Infection and Immunity

SN - 0019-9567

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