Murine trypanosomiasis recapitulates transcriptomic features of acute kidney injury

The African trypanosome, Trypanosoma brucei, disseminates systemically in tissues of the infected host resulting in complex immunopathology. The kidneys which are important in the response to the anaemia characteristic of African trypanosomiasis, are prone to acute kidney injury (AKI) from multiple noxious stimuli. Little is known about the transcriptional responses of the kidney to trypanosome infection. To assess the tissue-specific response to infection with Trypanosoma brucei , we profiled the clinicopathologic and transcriptional responses of the kidney in BALB/C (susceptible) and C57BL/6 (tolerant) murine models, at early (7 dpi) and late (21 dpi) time points of infection. Trypanosomes in the renal interstitium, tubular necrosis and inflammation characterised early infection in both mouse strains. By late infection, we observed extensive tubular necrosis in the susceptible BALB/C but reparative tubular regeneration in the tolerant C57BL/6 mice. T.b. brucei infection resulted in significant increases in serum creatinine in both strains. Consistent with the clinicopathologic findings, RNA-seq detected both mouse strain- and time-dependent transcriptional responses in the kidney. These included perturbations in genes associated with solute/ion transport, upregulation of markers of tubular injury, hypoxia, glycolysis, and a profound inflammatory and immune response, mirroring the responses observed in other models of AKI. Differential tissue pathology at late time point is preceded by expansion of CD8+ T cells, profound expression of transcription factors and upregulation of anti-inflammatory pathways in C57BL/6 mice. Our findings demonstrate that experimental T. brucei infection-induced kidney injury (TIKI) is a model of AKI and may have clinical implications for Human African Trypanosomiasis cases, who currently are not routinely screened for markers of kidney function. ### Competing Interest Statement The authors have declared no competing interest.