Speaker: Dr Tonia Woodbury
Dendritic cells (DC) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. In human blood there are two main subsets: myeloid DC (mDC) and plasmacytoid DC (pDC). Malaria caused by Plasmodium compromises DC but in asymptomatic infection (with a lower parasite biomass) DC appear to retain function. To determine whether low parasite biomass is key to the retained function, we evaluated DC in healthy volunteers before and after intra-venous inoculation with Plasmodium infected RBC (pRBC). A first sub-microscopic P. falciparum (Pf) or P. vivax (Pv) infection compromised the maturation of three blood DC subsets (CD1c+mDC, CD141+mDC and pDC) and activated CD16+ mDC. Only the activated CD16+ mDC spontaneously produced TNF and IL-12. CD1c+mDC and pDC produced cytokines upon TLR or pRBC stimulation. CD1c+mDC were most compromised by early infection as they failed to upregulate HLA-DR after stimulation. We conclude that sub-microscopic Plasmodium infection activates CD16+ mDC and compromises circulating CD1c+mDC, CD141+mDC and pDC. The maintenance of DC function in asymptomatic infection is not due to only low parasite biomass. Asymptomatic infection is contingent and possibly reliant upon appropriate DC maturation and function.