Roles of IgM in immunity to malaria in humans

A key mediator of protective immunity to malaria is antibodies that block merozoite invasion of the RBC. We have shown that human antibodies promote complement deposition on the merozoite surface to block RBC invasion. The majority of studies on human immunity and complement fixation have focused on the role of IgG whereas the role of IgM remains undefined. However, IgM has high capacity to mediate complement fixation. IgM is commonly thought to be a short lived antibody response which is replaced by IgG as protective immunity develops.  However, a number of studies suggest that this may not be the case in malaria. To define the potential role of IgM, we used multiple human cohorts to assess the dynamics of malaria-specific IgM during experimentally-induced and naturally acquired malaria, and identify the functional activity of IgM against blood stage parasites. We found that merozoite-specific IgM is rapidly acquired in P. falciparum infection, but is also a prominent response during malaria in children and adults with life-time exposure. IgM blocked merozoite invasion of RBCs in a complement-dependent manner. These findings suggest merozoite-specific IgM is an important functional and long-lived antibody response targeting blood-stage malaria parasites that contributes to malaria immunity.

Dr Boyle completed her PhD in 2012 at the University of Melbourne and Burnet Institute in malaria parasitology and immunology. She undertook postdoctoral training at the University of California San Francisco before returning to Australia and working on collaborative projects between the Menzies Institute, Darwin and Burnet Institute, Melbourne. She has recently joined QIMRB as an EMBL Australia group leader. Her group is focused on understanding the development of anti-parasitic and tolerogenic immune responses to malaria in humans.