Neutrophil metalloproteinase driven spleen architecture breakdown hampers plasma cell generation and infection control of trypanosomiasis.

Recent blood transcriptomic analysis of rhodesiense sleeping sickness patients has revealed that neutrophil signature genes and activation markers constitute the top indicators of trypanosomiasis-associated inflammation. Here, we used single cell RNA sequencing (scRNA-seq) to analyze the diversity of neutrophils in the spleen. We show that Trypanosoma brucei infection results in expansion and differentiation of four splenic neutrophil subpopulations, including Mki67+Birc5+Gfi1+Cebpe+ proliferation-competent precursors, two intermediate immature subpopulations and Cebpb+Spi1+Irf7+Mcl1+Csf3r+ inflammation reprogrammed mature neutrophils. Transcriptomic scRNA-seq profiling identified the largest immature subpopulation by Mmp8/9 positive tertiary granule markers. Overall design: Spleen were isolated from mice non-infected and 14 day post infected by T. brucei. brucei Antat1.1E, homogenized, then red blool cells lysis and analyzed using scRNAseq. The Naive dataset included in this repository was generated from an experiment that was specifically designed to be paired and performed alongside the T.b.brucei 14 dpi infected sample. The aim of this paired experiment was to study the response of the immune system, to the infection caused by T.b.brucei)