Poster Presentation First Malaria World Congress 2018

Activation of non-classical dendritic cells in controlled human malaria infection studies with Plasmodium falciparum (#332)

Jessica R Loughland 1 , Tonia Woodberry 1 2 , Michelle J Boyle 1 3 , Peta E Tipping 4 , Kim A Piera 1 , Fiona H Amante 5 , Christian R Engwerda 5 , Nick M Anstey 1 4 , James S McCarthy 5 6 , Gabriela Minigo 1 6
  1. Menzies School of Health Research, Darwin, NT, Australia
  2. Australian National University, Canberra, ACT, Australia
  3. Burnet Institute, Melbourne, VIC, Australia
  4. Royal Darwin Hospital, Darwin, NT, Australia
  5. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  6. equal, contribution

Dendritic cells (DCs) are professional antigen presenting cells and immune sentinels. Human DCs are composed of two classical DC subsets; DC1 (CD141, BDCA-3)+ and DC2 (CD1c, BDCA-1)+, as well as a third non-classical DC subset characterised by the expression of CD16 (FcγRIII). Non-classical DCs comprise half the DC compartment in humans, yet few studies have investigated their function. We evaluated CD16+ non-classical DC function in controlled human malaria infection (CHMI) studies with Plasmodium falciparum. In malaria-naive adult CHMI volunteers peripheral blood, non-classical DCs were examined before and after P. falciparum infection. Cytokine production (TNF, IL-12 and IL-10) was quantified ex vivo and in response to stimulation with toll like receptor (TLR) ligands and P. falciparum-infected red blood cells. DC number and maturation (HLA-DR, CD86) were also assessed. In response to TLR stimulation, non-classical DCs produced high levels of TNF and low levels of IL-12 and IL-10. In response to in vitro stimulation with P. falciparum-infected RBC, non-classical DCs increased co-production of TNF and IL-10. During CHMI, non-classical DCs significantly increased both TNF production and co-production of TNF and IL-10. Re-stimulation with P. falciparum-infected RBC further increased IL-10 production. In addition to enhanced cytokine production, CD16+ non-classical DCs also increased expression of HLA-DR and CD86 during CHMI. Together, these findings demonstrate that CD16+ non-classical DCs are uniquely activated and key responders early during P. falciparum infection.