Role of chemokines and cytokines in the neuropathogenesis of African trypanosomiasis

Abstract

Trypanosoma brucei spp. cause human African trypanosomiasis (HAT) or sleeping sickness in humans and nagana in animals. The early stages of the disease have no specific symptoms; however, the late stage of the disease involves neurological signs of the disease, including disturbance of sleep patterns from which the disease derives the name sleeping sickness. During the late stage of African trypanosomiasis parasites, increased numbers of white blood cells and levels of cytokines and/or chemokines are found in the brain parenchyma and/or cerebrospinal fluid of animal models and HAT patients. In this mini review, contemporary findings on how chemokines and cytokines are thought to play an important role in the central nervous system invasion by the parasites, inflammation and the neuropathology of the disease are discussed. The levels of various cytokines and chemokines, such as interferon-gamma (IFN-γ), interleukin-1 beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), C-C motif chemokine 2 (CCL2), CCL3, C-X-C motif chemokine 8 (CXCL8, IL-8) and CXCL10, in the cerebrospinal fluid (CSF) of HAT patients correlate with the severity or stage of the disease. Thus, these molecules are possible candidates for differentiating between early and late stage HAT. The role of cytokines and chemokines in parasite invasion of the central nervous system is also being elucidated. IFN-γ, TNF-α and CXCL-10 are some of the cytokines and chemokines now known to facilitate parasite penetration of the brain parenchyma. Interestingly, they also constitute some of the candidate molecules with potential to differentiate between stage 1 and 2 of HAT. The increased levels of cytokines, such as IL-1β, IL-6, IFN-γ and TNF-α, as well as prostaglandins, during African trypanosomiasis might contribute to the neurological dysfunctions that occur during HAT.

Keywords: African trypanosomiasis, Chemokine, Cytokine, Central nervous system, Brain parenchyma, Cerebrospinal fluid, Neuroinvasion, Neuroinflammation, Neurological disturbances

Core tip: Human African trypanosomiasis (HAT) or sleeping sickness, caused by Trypanosoma brucei spp., is staged into an early hemolymphatic stage and a late meningoencephalitic stage. During the late stage parasites, increased numbers/levels of white blood cells, cytokines and/or chemokines are found in the cerebrospinal fluid of patients. In this mini review, contemporary findings on how chemokines and cytokines, such as interferon-gamma (IFN-γ), TNF-α, C-X-C motif chemokine 8 (CXCL8) and CXCL10, are thought to play an important role in the central nervous system invasion by the parasites, inflammation and the neuropathology of the disease and what might be candidates to differentiate between early and late stage HAT are discussed.