Roles of cytokines in modulating Trypanosoma brucei rhodesiense infection outcomes in vervet monkeys

Abstract

Human African trypanosomiasis (HAT), caused by Trypanosoma brucei rhodesiense, remains a threat in east and southern African regions. The disease is widely categorised as acute, but often presents varying clinical outcomes that could also be considered as chronic. Although the mechanisms underpinning these variable clinical dynamics are poorly understood, host and parasite factors or both have been suggested. Here we assessed the roles of host cytokines in disease progression using a non-human primate (NHP), vervet monkey (Chlorocebus aethiops) model of HAT. We quantified the levels of eight cytokines, including TNF-α, IFN- γ, IL-10, IL-6, IL-12 and IL-1 β, the brain injury biomarker S100β, clinical data and compared acute and chronic infections. As expected, cytokine levels in both infected groups were significantly higher than uninfected controls (P<0.05). IL-12, IL-6 and IL-1β cytokines were significantly elevated (p < 0.05) in early-stage disease which extended from infection to the onset of late stage disease at a median (range) time of 16 (8-24) and 16 (12-28) dpi for acute and chronic strains respectively. IL-1β, IL-6, IL-12 and IL-10 are implicated in pro- and counter inflammatory responses and their modulation. C. aethiops infected with KETRI 3801 died with a mean survival time of 28 days compared to KETRI 3928 with a mean survival time of 95 days. In addition, CSF parasite and WBC levels were higher in KETRI 3801 as compared to KETRI 3928 infections. We conclude that cytokines play a role in modulating disease progression and severity in a NHP model of T. b. rhodesiense HAT. Further, we validate the cyclic vervet monkey model of HAT, enhancing its utility for disease pathogenesis studies. These results are important in investigating host-pathogen interactions to unravel varying infection outcomes.