African Sleeping Sickness: Trypanosome Invasion Mechanism

Entry and Attack

Entry Within the Mammalian Host

The initial contraction of sleeping sickness comes from the tsetse fly. This insect vector shares the trypanosome cell with its host through an unwarranted exchange. The fly injects its tube like mouth through the skin of the mammal and by the transmission of their saliva, directly inserts the dangerous cells into the host bloodstream. [7] This mechanism is how trypanosoma was initially shared with mammalian species, however this is not the only way that a person can be infected. Because the cell uses the host bloodstream for travel throughout the body, the disease will infect a developing fetus at any point within the host’s pregnancy. [11] As problematic as this microbe is for growing humans, it is even more dangerous to a developing fetus. Trypanosoma cells have also, in some cases, been found to be transmitted through sexual contact. However, this portal of entry has yet to be fully discovered.

Attack through the blood and nervous system

The initial attack of T. Brucei occurs within the blood vessels. The cells begin to push themselves through the capillary beds of the host epithelial cells causing deep lesions. [9] The goal at this point in the life cycle is to relocate within larger, more favorable blood vessels. These would include any blood vessel that leads to larger organ systems such as the spinal cord. After the lesions have persisted for a few days, the lymph nodes of the host begin to drain in attempt to clear the body of infection allowing the microbes to travel through them, infecting the lymphatic system. [9] This is the point of the life cycle that initiates symptoms such as headache, fever, fatigue, etc. These symptoms are caused by the trypanosoma microbes invading and than consuming the lymphatic system cells. The infection of the lymphatic system causes an identifiable sequelae: The swelling of a lymph node around the trapezius of the host often referred to as “Winterbottom’s sign”. [9]

The ultimate goal of the microbe T. brucei is to reach the brain through a variety of flowing parts of the body such as the bloodstream and spinal fluid. The cell’s traveling process to inhabit brain matter takes around fifty days. Research done by neuroscience faculty at the Karolinska Institute in Stockholm, Sweden studied mice to understand at what points the trypanosoma cell became fully immersed into the brain tissue of the host. [13] By the twelfth day of the study, researchers found the microbe within the blood capillaries of the brain, with only the occasional parasite found living outside of the vessel walls. At day forty-two, the experimenters began to see trypanosoma frequently throughout the parenchyma. The amount of cells within this location had only increased by day fifty of the study. Once within the parenchyma, the cells were most often found within the white matter of the brain, opposed to the cerebral cortex. [13] The white matter is the deeper tissue parts of the brain. This part of the brain is described to be primarily composed of the axons of neurons, which function to send electrical signals from one neuron to the next It only took an additional five days for these parasitic microbes to move from the white matter to the septal nuclei, confined primarily to the brain parenchyma. It was noted that an remarkable abundance of the found cells were surrounding very large vessels of these nuclei.

The largest research question surrounding the inoculation of brain tissue with T. brucei has to do with how this large cell can pass the blood brain barrier, otherwise known as the main filtering system between the brain and capillaries. The blood brain barrier (BBB) is extremely selective in what it allows to pass towards the brain. This structure is one within the human body that has the most security, yet continuously is deceived and allows T. brucei to pass leading to fatality. There are a great variety of theories on how this exchange occurs, but one appears to be more likely than the rest. Using a model system, brain microvascular endothelial cells (BMECs), experimenters found that the passage of the microbe likely has something to do with calcium channels. With the presence of the trypanosome microbe, the BMECs increased greatly in their oscillatory Ca²⁺ levels. This indicated the possibility that these microbes can alter the integrity of the monolayers within the BBB. These clear increases can be dictated by either a living T. Brucei cell or even by their secretions. These cells depend largely on the presence of cysteine protease in relationship with the barrier in order to control its permeability. These complexes likely are the structures that recruit these internal calcium ions. The effectiveness of passing by the microbe has been related to the strength of their cysteine proteases. Currently, the signals and responses that these proteases send have yet to be fully clarified. However, they are very important target locations for antibiotic treatment.