By using a strain of mice that mimics many of the features of the human immune system and can be infected with the most common human form of the malaria parasite, a team of scientists has identified a key host defense mechanism.
Over the past several years, lead author Jianzhu Chen, the Ivan R. Cottrell Professor of Immunology, a member of MIT's Koch Institute for Integrative Cancer Research, and colleagues have developed strains of mice that have the human cells necessary for a comprehensive immune response.
To generate these cells, the researchers deliver human hematopoietic stem cells, along with cytokines that help them mature into B and T cells, natural killer (NK) cells, and macrophages- all critical components of the immune system.
To adapt the mice for the study of malaria, the researchers injected them with human red blood cells every day for a week, at which point 25 percent of their red blood cells were human- enough for the malaria parasite to cause an infection.
The researchers investigated the role of NK cells and macrophages during the first two days of malaria infection. They found that eliminating macrophages had very little impact on the immune response during those early stages.
However, in mice lacking NK cells, parasite levels went up sevenfold, suggesting that NK cells are critical to controlling infection early on.
The researchers also identified a cell adhesion protein called LFA-1 that helps NK cells bind to red blood cells.
The study is published in proceedings of the National Academy of Sciences.
