An Overview of Trypanosoma brucei Infections: An Intense Host-Parasite Interaction

Abstract

Trypanosoma brucei rhodesiense and T. brucei gambiense, the causative agents of Human African Trypanosomiasis, are transmitted by tsetse flies. Within the vector, the parasite undergoes through transformations that prepares it to infect the human host. Sequentially these developmental stages are the replicative procyclic (in which the parasite surface is covered by procyclins) and trypo-epimastigote forms, as well as the non-replicative, infective, metacyclic form that develops in the vector salivary glands. As a pre-adaptation to their life in humans, metacyclic parasites begin to express and be densely covered by the Variant Surface Glycoprotein (VSG). Once the metacyclic form invades the human host the parasite develops into the bloodstream form. Herein the VSG triggers a humoral immune response. To avoid this humoral response, and essential for survival while in the bloodstream, the parasite changes its cover periodically and sheds into the surroundings the expressed VSG, thus evading the consequences of the immune system activation. Additionally, tools comparable to quorum sensing are used by the parasite for the successful parasite transmission from human to insect. On the other hand, the human host promotes clearance of the parasite triggering innate and adaptive immune responses and stimulating cytokine and chemokine secretion. All in all, the host-parasite interaction is extremely active and leads to responses that need multiple control sites to develop appropriately.

Keywords: antigenic diversity; dynamic interaction; host response; human African trypanosomiasis; variant surface glycoprotein.

FIGURE 1

Clinical presentation of HAT. The painful (infected) tsetse bite leads to the appearance of the so-called chancre. Two or three weeks later the disease evolves into two successive clinical stages. The hemolymphatic stage I is characterized by the appearance of intermittent fever episodes, adenopathies, splenomegaly, and even hepatic disturbances. Painful lymph nodes also occur at this stage. The meningoencephalitic stage II appears slowly over a period of months or years, depending on the infecting trypanosome. The parasites cross the blood brain barrier to infect the CNS, causing the appearance of the neurological manifestations characteristic of HAT, like disturbance to the patient’s sleep patterns, confusion and difficulty with coordination. At the terminal phase of the disease, disturbances in consciousness and the development of dementia with incoherence, double incontinence and epileptic seizures are common.

FIGURE 2

The changing aspects of VSG expression. Trypanosomes oscillate between distinct life stages. Metacyclic (VSG [+]) parasites become proliferative slender (VSG [+]) forms in the blood stream, reach G1/G0 phase and differentiate to non-proliferative, transmissible, stumpy, G0 arrested, VSG [+] forms. Stumpy forms only transform efficiently within the tsetse midgut to procyclic epimastigote forms (VSG [-]). VSG is constantly changed in each transmission cycle. This strategy represents an advantage for the parasite that the human immune system cannot control and thus warrants the parasite successful evasion of the immune system surveillance.

FIGURE 3

Proposed steps on Slender, Stumpy, Procyclic progression. Framework for the successive progression of trypanosomes from slender to stumpy to procyclic stages. The figure summarizes the data proposed by Engstler and Boshart (2004), Engstler et al. (2007), Figueiredo et al. (2008), Hertz-Fowler et al. (2008), Field and Carrington (2009), Horn (2014), and Mony and Matthews (2015).

FIGURE 4

Overview of the lively host–parasite-vector interaction in Trypanosoma brucei infections. The figure summarizes the dynamics of host–parasite interaction emphasizing the role of the immune system both of the human host and the vector. For details please see main text.