Interleukin 21 is a marker of Human African Trypanosomiasis Infection and a contributor to pathology in mice

BackgroundHuman African trypanosomiasis (HAT) is an important disease of sub-Saharan Africa that is approaching elimination in many regions. However, the disease has previously returned from similarly low case numbers in the past, making it important to identify issues that hinder elimination efforts. One important factor is likely to be the recent characterization of individuals with latent HAT infections that are able to tolerate HAT with few symptoms and to control blood parasitaemia to levels that are undetectable by microscopy. Although animal trypanotolerance has been examined in detail, it is unclear how the latent phenotype is maintained in humans. MethodsTo identify immune components involved in latent HAT, we used targeted RNASeq to examine the expression of 495 immune-related transcripts in blood collected from 287 individuals at active disease foci in Guinea. These samples included latent infections, HAT clinical cases, and uninfected controls. The in vivo effects of IL21 functional blockade was investigated using a murine model of trypanosomiasis. ResultsDifferential expression analysis revealed transcripts involved in T cell activation and B cell development that associated with trypanosome infection, including PD1, CD70, and CD80. In particular, IL21 was found to be elevated in infected individuals, although it was significantly higher in clinical cases relative to latent infections. This pattern was replicated at the protein level when patient sera were examined by ELISA. Reducing IL21 pathway activity in mice infected with Trypanosoma brucei led to increased survivorship and reduced parasitaemia in the model animals. ConclusionOur data show that IL21 is a potential biomarker of Human African Trypanosomiasis and is a cause rather than a consequence of symptoms severity. Further investigation of IL21 will contribute to understanding the factors involved in developing latent HAT, improving control efforts to identify and predict such infections. In the future, the factors identified in this study may also serve as intervention targets to control the symptoms of trypanosomiasis.