Hijacking red blood cells allows parasite to escape
Researchers discovered that the parasite Babesia microti uses red blood cells to migrate. It may be a way to evade the immune system and find new space to multiply.
Looking at a sample of parasite-infected blood, researchers at Carnegie Mellon University noticed the unexpected movement of red blood cells. Due to their simple structure, red blood cells are unable to move on their own. So what was happening to them?
Like someone stealing a car to flee from the police, the parasite Babesia microti uses red blood cells to migrate. The newly discovered phenomenon may be a way for it to hide and escape from white blood cells, which do not typically attack red blood cells.
When it enters the bloodstream and invades red blood cells, the parasite causes the infection Babesiosis, with symptoms similar to malaria. It is transmitted by tick bite, and cases are becoming more common in the Northeast, Mid-Atlantic, and Upper Midwest United States.
Because Babesia microti and other parasites are difficult to study in the lab, Tagbo Niepa and Chao Li built a microfluidic system for monitoring infected blood. Their μ-Blood platform makes it easier to study the life cycle of the parasite outside of the host system and watch its behavior over time.
Movement tracking trajectory of a B. microti-infected RBC propelled by the parasite.
Niepa, an associate professor of chemical engineering and biomedical engineering, and Li, a research scientist in the Niepa μBiointerface Lab at the time, were using their μ-Blood platform when they observed infected red blood cells moving on their own. “What’s intriguing is that the movement doesn’t originate from the red blood cells. The parasite somehow influences the host cell to move, likely as part of its strategy for survival and dissemination throughout the body,” says Li.
In PNAS, Niepa, Li, and their collaborators introduce a new, intermediate stage in the development of the parasite Babesia microti.
Bright-field and fluorescence confocal images (with 3D view) of PKH67-stained uninfected (A) and infected (B) RBC cytoplasm membranes and B. microti parasite cytoplasm membranes.
“This parasite is taking advantage of us in a way that’s sneaky and smart. It’s using a red blood cell as an invisibility cloak, and the immune system doesn’t recognize it,” says Amy Apgar. Apgar, a Ph.D. student in biomedical engineering, used scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescent confocal microscopy images to characterize the red blood cells in their experiments. Her images were key to verifying that the cells they observed moving were actually red blood cells infected with parasites and not white blood cells that already had motility.
The movement of red blood cells displays the parasite’s ability to alter host cell behavior. Evading the immune system is only one possible motivation. Triggering propagation is another. “Imagine that the motion allows the parasite to sense where there's a new area with fresh blood to infect,” says Niepa. The discovery reveals more about what parasites can do to relocate and find new space, away from the immune system, where they can easily multiply.
Transmission electron microscope image (A) and scanning electron microscope image (B) of uninfected RBCs. Transmission electron microscope image of B. microti-infected RBCs, each with a single parasite inside (C), and scanning electron microscope image of B. microti-infected RBCs with a buildup of fibrin and an increased amount of nanopores in the cytoplasm membrane (D).
“This is an important step forward in understanding how Babesiosis infections work and how we might combat them,” says Li. More insight into pathogen-host interactions could lead to innovative approaches for prevention or treatment. Niepa and Li’s findings also open new avenues to studying co-infections, such as those involving the parasite that causes Babesiosis and the bacteria responsible for Lyme disease.
This research was supported by the National Institute of General Medical Sciences of the United States National Institutes of Health (NIH), Grant No. 7DP2GM149553-02, and the National Science Foundation (NSF) Graduate Research Fellowship Program, Grant No. DGE2140739. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF or the NIH.