IL-4Rα signalling and Iloprost treatment modulate neuroimmune and neurocognitive responses in Trypanosoma brucei-Infected mice.

Despite the long-standing recognition of the impact of trypanosomiasis on brain functions, efforts to link the associated disease pathology to neuroinflammation and cognitive deficits have been largely unsuccessful, with trypanocidal drugs often proven ineffective. In this study, using novel object recognition task for recognition memory, we compared interleukin-4 receptor alpha-inhibited mice with trypanosome infection. Furthermore, we treated with Iloprost, a prostacyclin analogue, and the standard drug Diminazene aceturate subsequently for changes in transcriptional expressions of IL-4 and IL-13. Given the role of IL-4 in cognitive learning and the established anti-inflammatory effects of Iloprost, we hypothesized that Iloprost treatment could enhance IL-4/IL-13 signalling via IL-4Rα, thereby mitigating cognitive deficits associated with CNS trypanosome infection. This study revealed that Iloprost modulates the neuroimmune response of IL-4Rα, thereby influencing the IL-4 and IL-13 mRNA expressions. This study suggests that Iloprost plays a role in suppressing the neurocognitive response of Trypanosomiasis in mice. Our findings indicate that the prostacyclin analogue (Iloprost) potentiates the IL-4Rα pathway through the upregulation of IL-13 and IL-4 signalling. These activated signalling pathways might contribute to the protective effects of Iloprost on cognitive impairment in trypanosomiasis.