Intracellular Eimeria bovis macromeront formation induces bystander cell accumulation and TNT formation

Jobst Fischer^*Lara SousZahady VelásquezCarlos HermosillaAnja Taubert

• Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, Giessen, Germany

First merogony of the intracellular parasite Eimeria bovis is a long-lasting process resulting in the formation of large macromeronts. The production of > 140,000 merozoites I causes metabolic stress in host cells, finally resulting in mitochondrial dysregulation and premature senescence. Here, we detected a significant accumulation of non-infected bystander cells around E. bovis macromeront-carrying host cells (MCHCs), eventually supporting MCHCs. Thereby, different primary cell types proved capable as bystander cells. Of note, healthy cells may revitalize stressed cells by donating mitochondria via tunnelling nanotubes (TNTs). Here, TNT quantification revealed an upregulation of these structures by E. bovis infection. Moreover, low-dose cytochalasin B treatments blocked TNT formation and dampened parasite proliferation. Furthermore, we observed bidirectional mitochondrial transfer between non-infected and E. bovis-infected cells, thereby potentially helping to restore the energetic status of the infected host cell. Overall, bystander cell-based TNT-mediated mitochondria transfer may evidence a new mechanism of parasite-induced host cell modulation, aiding MCHCs to recover to a normal operating state.