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

• Authors: Jessica R Loughland, Gabriela Minigo, Julie Burel, Peta E Tipping, Kim A Piera, Fiona H Amante, Christian R Engwerda, Michael F Good, Denise L Doolan, Nicholas M Anstey, James S McCarthy, Tonia Woodberry
• Journal: Infection and immunity (Infect Immun) Vol. 84 Issue 5 Pg. 1403-1412 (05 2016) ISSN: 1098-5522 [Electronic] United States
• PMID: 26902728 (Publication Type: Journal Article)
• Copyright: Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Chemical References

• Antigens, CD1
• B7-2 Antigen
• CD1C protein, human
• CD86 protein, human
• Glycoproteins
• HLA-DR Antigens
• TNF protein, human
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Antigens, CD1 (analysis)
• B7-2 Antigen (analysis)
• Cohort Studies
• Dendritic Cells (chemistry, immunology)
• Female
• Glycoproteins (analysis)
• HLA-DR Antigens (analysis)
• Healthy Volunteers
• Humans
• Malaria, Falciparum (pathology)
• Male
• Plasmodium falciparum (immunology)
• Tumor Necrosis Factor-alpha (metabolism)
• Young Adult