AUTHOR=Hou Zhaofeng , Wang Lele , Su Dingzeyang , Cai Weimin , Zhu Yu , Liu Dandan , Huang Siyang , Xu Jinjun , Pan Zhiming , Tao Jianping 

TITLE=Global MicroRNAs Expression Profile Analysis Reveals Possible Regulatory Mechanisms of Brain Injury Induced by Toxoplasma gondii Infection

JOURNAL=Frontiers in Neuroscience

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.827570

DOI=10.3389/fnins.2022.827570

ISSN=1662-453X

ABSTRACT=<p><italic>Toxoplasma gondii</italic> (<italic>T. gondii</italic>) is an obligate intracellular parasitic protozoan that can cause toxoplasmosis in humans and other endotherms. <italic>T. gondii</italic> can manipulate the host gene expression profile by interfering with miRNA expression, which is closely associated with the molecular mechanisms of <italic>T. gondii</italic>-induced brain injury. However, it is unclear how <italic>T. gondii</italic> manipulates the gene expression of central nervous system (CNS) cells through modulation of miRNA expression <italic>in vivo</italic> during acute and chronic infection. Therefore, high-throughput sequencing was used to investigate expression profiles of brain miRNAs at 10, 25, and 50 days post-infection (DPI) in pigs infected with the Chinese I genotype <italic>T. gondii</italic> strain in this study. Compared with the control group 87, 68, and 135 differentially expressed miRNAs (DEMs) were identified in the infected porcine brains at 10, 25, and 50 DPI, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that a large number significantly enriched GO terms and KEGG pathways were found, and were mostly associated with stimulus or immune response, signal transduction, cell death or apoptosis, metabolic processes, immune system or diseases, and cancers. miRNA–gene network analysis revealed that the crucial connecting nodes, including DEMs and their target genes, might have key roles in the interactions between porcine brain and <italic>T. gondii</italic>. These results suggest that the regulatory strategies of <italic>T. gondii</italic> are involved in the modulation of a variety of host cell signaling pathways and cellular processes, containing unfolded protein response (UPR), oxidative stress (OS), autophagy, apoptosis, tumorigenesis, and inflammatory responses, by interfering with the global miRNA expression profile of CNS cells, allowing parasites to persist in the host CNS cells and contribute to pathological damage of porcine brain. To our knowledge, this is the first report on miRNA expression profile in porcine brains during acute and chronic <italic>T. gondii</italic> infection <italic>in vivo</italic>. Our results provide new insights into the mechanisms underlying <italic>T. gondii</italic>-induced brain injury during different infection stages and novel targets for developing therapeutic agents against <italic>T. gondii</italic>.</p>