Systems analysis shows a role of cytophilic antibodies in shaping innate tolerance to malaria

Natural immunity to malaria develops over time with repeated malaria episodes, but protection against severe malaria and immune regulation limiting immunopathology, called tolerance, develops more rapidly. Here, we comprehensively profile the blood immune system in patients, with or without prior malaria exposure, over 1 year after acute symptomatic Plasmodium falciparum malaria. Using a data-driven analysis approach to describe the immune landscape over time, we show that a dampened inflammatory response is associated with reduced gamma delta T cell expansion, early expansion of CD16(+) monocytes, and parasite-specific antibodies of IgG1 and IgG3 isotypes. This also coincided with reduced parasitemia and duration of hospitalization. Our data indicate that antibody-mediated phagocytosis during the blood stage infection leads to lower parasitemia and less inflammatory response with reduced gamma delta T cell expansion. This enhanced control and reduced inflammation points to a potential mechanism on how tolerance is established following repeated malaria exposure.

Automated summary

This study comprehensively profiles the immune system of patients with acute symptomatic Plasmodium falciparum malaria over a year. The results indicate that a dampened inflammatory response is associated with reduced expansion of gamma delta T cells, early expansion of CD16(+) monocytes, and production of specific antibodies. This control of infection and reduction of inflammation suggest a potential mechanism for the establishment of tolerance following repeated malaria exposure.