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Credit: Bjorn Onfelt/Dan Davis
The parasites that cause malaria are adapted to the hosts they infect, so studying the disease in mice doesn’t necessarily reveal information that translates to human disease.
But scientists believe they may have overcome this limitation. They’ve developed a strain of mice that mimics many features of the human immune system and can be infected with Plasmodium falciparum.
Using this strain, the researchers discovered that natural killer (NK) cells preferentially interact with and kill infected red blood cells (RBCs) in a contact-dependent manner.
The group recounted this discovery in PNAS.
“Human malaria studies have been hampered by a lack of animal models,” said study author Jianzhu Chen, PhD, of the Singapore-MIT Alliance for Research and Technology in Singapore.
“This [research] paves the way to start dissecting how the host human immune system interacts with the pathogen.”
Scientists studying malaria in mice previously generated mice with human RBCs. But these mice have compromised immune systems, so they can’t be used to study the immune response to malaria infection.
Over the past several years, Dr Chen and his 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, NK cells, and macrophages. These mice have already proven useful to study other diseases, such as dengue fever.
To adapt the mice for the study of malaria, the scientists injected them with human RBCs every day for a week, at which point 25% of their RBCs were human. And this was enough for the malaria parasite to cause an infection.
The researchers investigated the role of NK cells and macrophages during the first 2 days of malaria infection. And 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 7-fold, suggesting that NK cells are critical to controlling infection early on.
To further investigate the role of NK cells, the scientists placed human NK cells in a sample of infected and uninfected RBCs. The NK cells randomly interacted with both types of cells, but they latched onto infected cells much longer, eventually killing them.
The researchers also identified a cell adhesion protein called LFA-1 that helps NK cells bind to RBCs. They are now studying this process in more detail and trying to determine what other molecules, including those produced by the malaria parasite, might be involved.
Dr Chen and his colleagues also hope to use these mice to study experimental malaria vaccines or drugs. And in another future study, they plan to inject the mice with RBCs from patients with sickle cell anemia to investigate how the sickle-shaped cells help people survive malaria infection. 
Credit: Bjorn Onfelt/Dan Davis
The parasites that cause malaria are adapted to the hosts they infect, so studying the disease in mice doesn’t necessarily reveal information that translates to human disease.
But scientists believe they may have overcome this limitation. They’ve developed a strain of mice that mimics many features of the human immune system and can be infected with Plasmodium falciparum.
Using this strain, the researchers discovered that natural killer (NK) cells preferentially interact with and kill infected red blood cells (RBCs) in a contact-dependent manner.
The group recounted this discovery in PNAS.
“Human malaria studies have been hampered by a lack of animal models,” said study author Jianzhu Chen, PhD, of the Singapore-MIT Alliance for Research and Technology in Singapore.
“This [research] paves the way to start dissecting how the host human immune system interacts with the pathogen.”
Scientists studying malaria in mice previously generated mice with human RBCs. But these mice have compromised immune systems, so they can’t be used to study the immune response to malaria infection.
Over the past several years, Dr Chen and his 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, NK cells, and macrophages. These mice have already proven useful to study other diseases, such as dengue fever.
To adapt the mice for the study of malaria, the scientists injected them with human RBCs every day for a week, at which point 25% of their RBCs were human. And this was enough for the malaria parasite to cause an infection.
The researchers investigated the role of NK cells and macrophages during the first 2 days of malaria infection. And 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 7-fold, suggesting that NK cells are critical to controlling infection early on.
To further investigate the role of NK cells, the scientists placed human NK cells in a sample of infected and uninfected RBCs. The NK cells randomly interacted with both types of cells, but they latched onto infected cells much longer, eventually killing them.
The researchers also identified a cell adhesion protein called LFA-1 that helps NK cells bind to RBCs. They are now studying this process in more detail and trying to determine what other molecules, including those produced by the malaria parasite, might be involved.
Dr Chen and his colleagues also hope to use these mice to study experimental malaria vaccines or drugs. And in another future study, they plan to inject the mice with RBCs from patients with sickle cell anemia to investigate how the sickle-shaped cells help people survive malaria infection.
Credit: Bjorn Onfelt/Dan Davis
The parasites that cause malaria are adapted to the hosts they infect, so studying the disease in mice doesn’t necessarily reveal information that translates to human disease.
But scientists believe they may have overcome this limitation. They’ve developed a strain of mice that mimics many features of the human immune system and can be infected with Plasmodium falciparum.
Using this strain, the researchers discovered that natural killer (NK) cells preferentially interact with and kill infected red blood cells (RBCs) in a contact-dependent manner.
The group recounted this discovery in PNAS.
“Human malaria studies have been hampered by a lack of animal models,” said study author Jianzhu Chen, PhD, of the Singapore-MIT Alliance for Research and Technology in Singapore.
“This [research] paves the way to start dissecting how the host human immune system interacts with the pathogen.”
Scientists studying malaria in mice previously generated mice with human RBCs. But these mice have compromised immune systems, so they can’t be used to study the immune response to malaria infection.
Over the past several years, Dr Chen and his 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, NK cells, and macrophages. These mice have already proven useful to study other diseases, such as dengue fever.
To adapt the mice for the study of malaria, the scientists injected them with human RBCs every day for a week, at which point 25% of their RBCs were human. And this was enough for the malaria parasite to cause an infection.
The researchers investigated the role of NK cells and macrophages during the first 2 days of malaria infection. And 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 7-fold, suggesting that NK cells are critical to controlling infection early on.
To further investigate the role of NK cells, the scientists placed human NK cells in a sample of infected and uninfected RBCs. The NK cells randomly interacted with both types of cells, but they latched onto infected cells much longer, eventually killing them.
The researchers also identified a cell adhesion protein called LFA-1 that helps NK cells bind to RBCs. They are now studying this process in more detail and trying to determine what other molecules, including those produced by the malaria parasite, might be involved.
Dr Chen and his colleagues also hope to use these mice to study experimental malaria vaccines or drugs. And in another future study, they plan to inject the mice with RBCs from patients with sickle cell anemia to investigate how the sickle-shaped cells help people survive malaria infection.