A study by the University of Bonn and the Peter Doherty Institute for Infection and Immunity at the University of Melbourne announced on Aug. 4 that malaria infection causes permanent damage to resident CD163 macrophages in the spleen, which are responsible for cleaning blood, recycling iron, and communicating with other immune cells. The findings could have implications for more effective malaria vaccines as well as treatments for other infectious diseases. The research will be published in the journal "Immunity" and is already available online.
Macrophages play a key role in nonspecific defenses by removing pathogens, dead cells, and foreign substances from the body. Resident macrophages usually regenerate through cell division; however, when many are destroyed during severe infection or injury, bone marrow-derived white blood cells take over their function. "People used to assume that this replacement was virtually 1:1, but our latest research shows this not to be the case," said Mass.
The joint study with Dr. Lynette Beattie's group at the Doherty Institute examined how malaria affects resident macrophages in genetically altered mice. According to Mass, "The spleen is home to a large population of macrophages that eat dead red blood cells, recycling iron in the process. They possess a receptor called CD163." The researchers found that during malaria's blood stage—when fever occurs—the presence of parasites leads to long-lasting loss of CD163 macrophages; even months after infection subsides, these populations do not recover.
Mass said new bone marrow-derived cells replace lost CD163 macrophages but lack their specialization. This impacts not only scavenging functions but also immune signaling within the spleen: "This structure helps to make sure that the immune cells in the spleen can get the signals that they need to fight bacteria and viruses, and we found that this structure and the associated communication network is persistently damaged by malaria," said Dr. Beattie.
Further experiments showed eliminating a key signaling molecule shrinks marginal zone macrophage populations; depleting CD163 macrophages worsens infections by increasing parasite release into bloodstreams and prolonging anemia. Since these changes are persistent rather than temporary, repeated infections have significantly worse outcomes.
Mass concluded, "Our results indicate that a single malaria episode can leave a lasting impression on immunological memory, particle filtering and the spleen's iron metabolism." The international study included institutions from Australia, Portugal, France, China and Singapore with funding from several foundations.
