Bovine macrophages transcriptome profiling reveals divergent responses to virulent and attenuated Babesia bovis strains

Abstract

Babesia bovis is a tick-borne parasite of major economic impact in the livestock industry. Control strategies rely mainly on the use of acaricides and live attenuated vaccines. Comparative genomic analyses have shown no major differences between virulent and attenuated B. bovis strains, suggesting that studies on the host’s differential response may represent a key step toward clarifying the basis of disease severity and vaccine efficacy. In this study, we analyzed by RNA-seq the differential gene expression in bovine monocyte-derived macrophages after phagocytosis of erythrocytes infected with either the virulent B. bovis S2P strain or the attenuated R1A one. The results revealed a common transcriptional core response of several cellular processes largely centered on lymphocyte related functions, cytokine regulation, and adaptive immune signaling. In turn, the two strains elicited contrasting responses in bovine macrophages, where the virulent strain induced the enrichment of lymphocyte- and antiviral-related pathways, and the attenuated strain led to a stronger pro-inflammatory, chemotactic, and extracellular matrix remodeling signatures. Taken together, these data improved our understanding of the early transcriptional events that develop in macrophages in response to the phagocytosis of red blood cells containing contrasting B. bovis strains. This large dataset could be evaluated in further studies to better characterize the pathogenic mechanisms of bovine babesiosis and to identify targets for host-directed therapeutic strategies.