Temporal Dynamic Interplay of Mouse Proteome during Protozoan Babesia microti Infection Alone or with Borrelia burgdorferi Coinfection

Abstract

Apicomplexan protozoan parasite Babesia microti (Bm) and spirochete Borrelia burgdorferi are tick-transmitted pathogens that cause babesiosis and Lyme disease and increasingly cause coinfections. More pronounced Lyme arthritis occurs during the acute phase of coinfection compared to B. burgdorferi alone. In susceptible C3H mice, Bm parasitemia was quantified by microscopic examination of blood smears while live imaging of bioluminescent B. burgdorferi N40 strain-infected mice allowed monitoring of disseminated infection. Furthermore, proteomic analyses of blood samples unveiled nuanced temporal host gene expression. At 2 weeks postinfection, 31, 96, 76, and 22 unique proteins were detected in naïve and N40+Bm-, N40-, and Bm-infected mice, respectively, while 3359 common proteins were identified across all groups. The proteomic landscape showed a significant overlap between naive and Bm-infected mice with the most pronounced differences from the coinfected group. Using fold change scatter plots, upregulation of proteins associated with cellular and metabolic processes was noticed particularly in the coinfected mice. At 4 weeks, proteomic profiles among naive, Bm, and coinfection mice demonstrate distinct host responses in blood. The overlap diminished further at 16 weeks with stage-specific clustering of proteins observed. Our findings illustrate intricate interactions between these two pathogens and valuable host proteome dynamics during infection.