Science Bite (3 minute oral presentation with PPT in live session and poster) - Students and ECRs only Lorne Infection and Immunity 2023

Monocytes as effectors of antibody-mediated functions in malaria infection (#54)

Jessica Horton 1 , Jessica Loughland 2 , Megan Soon 2 , Daisy Mantila 3 , Shazia Ruybal-Pesántez 4 , Nicholas Dooley 2 , Julianne Hamelink 2 , Moses Laman 3 , Ivo Mueller 4 , Leanne Robinson 1 , Michelle Boyle 2 , James Beeson 1
  1. Burnet Institute, Melbourne, VIC, Australia
  2. QIMR-Berghofer Medical Research Institute, Herston, QLD
  3. Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
  4. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Monocytes are critical effector cells in malaria immunity and support parasite clearance via several mechanisms including antibody-mediated phagocytosis. While antibodies have long been established as vital to malaria immunity, a high antibody magnitude alone does not ensure clinical protection. An increasing body of evidence suggests antibody functional properties, such as complement fixation and the ability to bind Fcγ-receptors, are more meaningful measures of immunity acquired through natural exposure or vaccination. Defined correlates of malaria immunity have to date remained elusive, complicating analysis of vaccine efficacy in clinical trials, so the effects of these functional antibodies warrant further exploration. Monocytes are capable of phagocytosing blood stage malaria parasites (merozoites and infected red blood cells) opsonised with IgG and/or complement. Therefore, we investigated the surface expression of monocyte functional receptors in children in a malaria-endemic setting to better understand the interaction between antibodies, complement and monocytes in malaria immunity. Cells isolated from 80 participants in Papua New Guinea, comprising children with Plasmodium falciparum or P. vivax infection and children and adults without malaria infection, were analysed with spectral flow cytometry. While established markers of monocyte activation were not upregulated, we found that the expression of Fcγ-receptors, which enable phagocytosis of opsonized parasites, was increased on classical monocytes during infection. Key complement receptors were expressed by monocytes but were not upregulated during infection. P. falciparum and P. vivax infection modulated monocyte functional phenotypes in different ways. It was also evident that crucial functional markers on both monocytes and dendritic cells were differentially expressed in children compared to adults. This work reveals new insights on specific functional properties of monocytes relevant to their role as effectors of antibody-mediated parasite clearance in malaria infection and supports the investigation of Fcγ-receptor binding by antibodies and monocyte functions in ongoing vaccine studies.