Differential response of macrophages and neutrophils to trypanosome infections in zebrafish: occurrence of foamy macrophages

A tightly regulated innate immune response to trypanosome infections is critical to strike a balance between parasite control and inflammation-associated pathology. In the present study, we make use of the recently established Trypanosoma carassii infection model in larval zebrafish to study the early response of macrophages and neutrophils to trypanosome infections in vivo. We consistently identified high- and low-infected individuals and were able to simultaneously characterize their differential innate response. Not only did macrophage and neutrophil number and distribution differ between the two groups, but also macrophage morphology and activation state. Exclusive to high-infected zebrafish, was the appearance of macrophages rich in lipid droplets, confirmed to be foamy macrophages and characterized by a strong pro-inflammatory profile. Altogether, we provide an in vivo characterization of the differential response of macrophage and neutrophil to trypanosome infection and identify foamy macrophages as potentially associated with an exacerbated immune response and susceptibility to the infection. To our knowledge this is the first report of the occurrence of foamy macrophages during an extracellular trypanosome infection.