NK-, NKT- and CD8-Derived IFNy Drives Myeloid Cell Activation and Erythrophagocytosis, Resulting in XXXX .

@entity1 @entity32 @entity417 @entity19 @entity4409 @entity281 @entity1961 @entity5895 @entity25
African trypanosomes are the causative agents of @entity1 African Trypanosomosis ( @entity25 ) and @entity4409 (AAT/Nagana). A common hallmark of African trypanosome @entity281 is @entity32 . In @entity19 trypanosomosis, the onset of @entity32 occurs rapidly after @entity281 and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after @entity5895 , @entity417 develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing @entity417 . Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a @entity19 model for trypanosomosis. Results indicate that IFNy plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as @entity19 lacking the IFNy receptor were partially protected against @entity32 and @entity417 . NK and NKT cells were the earliest source of IFNy during T. b. @entity281 . Later in @entity281 , CD8+ and to a lesser extent @entity1961 + T cells become the main IFNy producers. Cell depletion and transfer experiments indicated that during @entity281 the absence of NK, NKT and CD8+ T cells, but not @entity1961 + T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNyR-/- @entity19 . Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNy is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute @entity32 -associated @entity417 .
