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

Loughland, Jessica R., Minigo, Gabriela, Burel, Julie, Tipping, Peta E., Piera, Kim A., Amante, Fiona H., Engwerda, Christian Rl, Good, Michael F., Doolan, Denise L., Anstey, Nicholas M., McCarthy, James S., and Woodberry, Tonia (2016) Profoundly reduced CD1c+myeloid dendritic cell HLA-DR and CD86 expression and increased tumor necrosis factor production in experimental human blood-stage malaria infection. Infection and Immunity, 84 (5). pp. 1403-1412.

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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.

Item ID: 46657
Item Type: Article (Refereed Research - C1)
ISSN: 1098-5522
Funders: Australian National Health and Medical Research Council (NHMRC), University of Queensland (UQ)
Projects and Grants: NHMRC 1021198, 1037304, NHMRC Fellowship, UQ International Scholarship
Date Deposited: 14 Dec 2016 02:26
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111716 Preventive Medicine @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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