Malaria parasite impairs key immune system cells

Plasmodium, the parasite responsible for malaria, impairs the ability of key cells of the immune system to trigger an efficient immune response. This might explain why patients with malaria are susceptible to a wide range of other infections and fail to respond to several vaccines. In a study published today in the open access journal Journal of Biology (http://jbiol.com/), researchers show that if dendritic cells, the key cells involved in initiating immunity, are exposed to red blood cells infected with Plasmodium chabaudi, they initiate a sequence of events that result in compromised antibody responses. The researchers show that this is due to the presence of hemozoin, a by-product of the digestion of hemoglobin by Plasmodium, in infected red blood cells. These observations also explain why vaccines for many diseases are so ineffective during malaria infection, and suggest that the use of preventive anti-malarial drugs before vaccination may improve vaccine-induced protection.

In a study funded by the Wellcome Trust, Owain Millington and colleagues from the University of Strathclyde, UK, studied the effects of Plasmodium chabaudi, the mouse Plasmodium, on mice antigen-presenting dendritic cells in culture and confirmed their findings in live mice.

Millington et al.'s results show that dendritic cells exposed to P. chabaudi–infected red blood cells do not activate normally. They express lower levels of membrane molecules that stimulate other cells of the immune system, and their cytokine production is lower than that of normal dendritic cells. Millington et al. demonstrate that this is caused by exposure to hemozoin present in infected red blood cells.

Millington et al. then show that P.chabaudi-infected dendritic cells fail to activate helper T cells properly – T cells are activated but show reduced proliferation and cytokine production in culture. Importantly, during malaria infection, T cells fail to migrate to B-cell areas of lymph nodes or spleen, and this results in the failure of B-cell activation and antibody production.

Article:
Suppression of adaptive immunity to heterologous antigens during plasmodium infection through haemozoin-induced failure of DC function
Owain R Millington, Caterina Di Lorenzo, R Stephen Phillips, Paul Garside & James M Brewer
Journal of Biology 2006,5:5 (12 April 2006)
http://jbiol.com/content/5/2/5

---

---