Immune Regulation and Immunopathology of Malaria

Most survivors in malaria endemic regions are able to develop partial immunity after repeated malaria infections throughout the years. This partial immunity protects them from developing severe complications, and they can survive with chronic asymptomatic infection. It is common to find sequestration of the Plasmodium parasites and the retention of the parasite byproducts, hemozoin, in various tissues in malaria patients. This raises the concern whether single infection or chronic asymptomatic infection imposes any risks in chronic tissue damage and immune dysregulation. The Plasmodium parasites invade the bone marrow that serves as a niche for gametocyte differentiation, and they leave their byproducts in the bone marrow. We previously reported that these Plasmodium products accumulate and persist in the bone marrow for a long time even after recovery from malaria infection. These parasite products induce chronic inflammation in the bone marrow and activate osteoclast resorption to cause bone loss with only a single infection. This suggests single malaria infection is sufficient to disrupt the crosstalk between bone and immune systems. It is still unclear why malaria survivors can only develop partial immunity and the only malaria vaccine exhibits limited efficacy. It is our interest to elucidate how malaria parasites evade host immunity and the chronic impact it leaves on the host immune system. Understanding immune regulation of malaria infection will help to set strategy for better intervention of the disease.