Red blood cells normally cannot move on their own; they lack any of the cell structures needed for movement. Instead, they deliver oxygen throughout the body by going with the flow of blood.
So, when researchers at Carnegie Mellon University who were testing a new tool for studying microbes in blood, saw these red blood cells moving on their own, they were shocked. But these were not just ordinary red blood cells, they were infected with the protozoan parasite Babesia microti.
In a recent study, Tagbo Niepa, a biomedical engineer at Carnegie Mellon University, and his team discovered that red blood cells infected with B. microti moved with distinct directionality.1 Unravelling if and how the parasites intentionally steer the cells may point to previously unknown molecules involved in infection and potential targets for treatment. They reported the finding in the Proceedings of the National Academy of Sciences.
Parasites like B. microti and its more famous malaria-causing relatives, Plasmodium, enter their hosts via a bite from a blood sucking arthropod. For B. microti the culprit is a tick. Once inside their host, the parasites enter red blood cells and feed on the hemoglobin inside.
Compared to malaria however, less is known about how Babesia species behave in mammalian hosts, in particular how it gets in and out of red blood cells, feeds, and replicates. According to Jan Perner, a tick biologist at the Biology Centre of the Czech Academy of Science who was not involved with the new study, this is because Babesia is mainly a veterinary concern.
“In the cattle industry it is a big issue,” said Perner. “It’s very serious, and the dynamics of the disease can be quite dramatic.”
However, Babesia species can also cause human disease with symptoms like fever, anemia, chills, and fatigue. Most cases are believed to be asymptomatic, but the disease can be severe for immunocompromised patients.
This disparity in knowledge is exactly why Niepa was designing a new tool called µ-Blood to study Babesia parasites in the blood. The tool allows researchers to observe the parasite in the blood for several days. They can see how the microbes move and quantify infection levels without the need for molecular biology techniques like PCR.
It was during tests of µ-Blood that they made the startling find. “This is a very unique phenomenon that we capture, where basically we can see the parasite moving the red blood cells around,” said Niepa.
In the blood of infected mice roughly one percent of infected cells were moving at speeds of two micrometers per minute, similar to the speed of macrophages.
To confirm that the parasite was controlling the movement, the team compared uninfected and infected blood in the µ-Blood system and clearly observed that the movement of red blood cells from infected animals was unique.
They then used a combination of cell staining along with confocal and bright field microscopy techniques to pinpoint where the parasites were located and how the cells moved. “When you combine that with other types of advanced imaging techniques, such as electron microscopy, then you have a good idea about what is happening, really that this is triggered by the parasite inside the red blood cells,” said Niepa.
In theory, the parasite may want to move the blood cells toward new cells to infect or evade the immune system. However, Perner added that the movement may not be purposeful. He said, “It can be going the other way, into the mouth of the macrophage.” To determine if this movement has purpose or is advantageous, more research is needed.
Niepa agreed. “If this is about escaping, then much more assays need to be done to understand, for instance, how they can sense the presence of white blood cells around them, and then what triggered that motion.”
For Gavin Wright, a molecular biochemist at the University of York who was unaffiliated with the study, “The next step would be to try and understand what the molecular mechanisms could be for this particular behavior.” The molecules involved could then point to a physiological role for the behavior or possible targets for treatments.
Both Wright and Perner agreed that it is an interesting finding, but there is a lot more work to do to before B. microti gets its driver’s license.
