Transcriptomic Analysis of Innate Immune Responses to Toxoplasma gondii in Bat Cells

Abstract

Bats exhibit remarkable tolerance to numerous viral infections, a phenotype associated with distinctive adaptations in innate immune and inflammatory pathways. Whether these adaptations also shape responses to nonviral intracellular pathogens remains poorly understood. Here, we investigated the interaction between the protozoan parasite Toxoplasma gondii and epithelial cell lines derived from the black flying fox (Pteropus alecto). We found that both type I and type II strains of T. gondii readily invaded and replicated in bat cells, demonstrating a high degree of cellular permissiveness to infection. Surprisingly, transcriptomic analysis revealed remarkably limited early host responses despite progressive intracellular parasite replication. A pronounced transcriptional response emerged only at later stages of infection, coinciding with extensive parasite replication and cellular damage, and was characterized by changes in genes associated with inflammatory signaling, metabolic adaptation, and tissue remodeling. Together, these findings reveal an unusual interaction between bat cells and an intracellular protozoan pathogen, characterized by efficient parasite replication and markedly delayed host transcriptional activation. Our results suggest that distinctive regulation of cellular responses to intracellular infection may extend beyond viral pathogens and represent a broader feature of bat immune biology.