<i>Neospora caninum</i> infection specifically suppresses the expression of a host lncRNA <i>XR_001919077.1</i> to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy

<i>Neospora caninum</i> is one of the most common pathogens causing reproductive failure in ruminants (e.g., cattle and goats) worldwide. However, due to a poor understanding of the pathogenic mechanisms of <i>N. caninum</i> infection, no effective drugs and vaccines are currently available. Long non-coding RNAs (lncRNAs) have been reported to be important regulators involved in a great number of physiological and pathological processes. Our previous study found that <i>N. caninum</i> infection induced significantly aberrant expression of lncRNA profiles in caprine endometrial epithelial cells (EECs). In the present study, we found that <i>N. caninum</i> infection specifically suppressed the expression of a novel lncRNA, <i>XR_001919077.1</i>, and knockdown of <i>XR_001919077.1</i> with small interfering RNA significantly promoted the propagation of <i>N. caninum</i> in caprine EECs. Rapid amplification of cDNA ends analysis generated six splice variants of <i>XR_001919077.1</i>, with lengths ranging from 592 to 694 nt. Transfection of the full length of each variant markedly inhibited the propagation of <i>N. caninum</i> in caprine EECs. Further study suggested that <i>XR_001919077.1</i> acted as a sponge of Chi-miR-93-5p to promote the expression of <i>sirt1</i>, and the <i>XR_001919077.1</i>/Chi-miR-93-5p/<i>sirt1</i> axis significantly delayed the <i>in vitro</i> growth of <i>N. caninum</i> in caprine EECs by regulating host cell mitochondrial function and autophagy. Our findings provide a novel insight to understand the interactions between <i>N. caninum</i> and host cells.IMPORTANCEThe uterus is an indispensable reproductive organ for embryo implantation and fetal growth. The endometrium is more vulnerable to infection by pathogenic microorganisms resulting in an increased risk of miscarriage. <i>Neospora caninum</i> is one of the most common pathogens causing miscarriage in ruminants and is able to naturally inhabit the uterus, with <i>N. caninum</i> tissue cysts found in the endometrium. Recent advances in <i>N. caninum</i> research have revealed aberrant expression of long non-coding RNA (lncRNA) profiles in infected caprine endometrial epithelial cells. In the present study, <i>N. caninum</i>, but not <i>Toxoplasma gondii,</i> which has similar morphological and biological features to <i>N. caninum</i>, specifically suppresses the expression of a host lncRNA, <i>XR_ 001919077.1</i>, to impair host's defense through the competitive endogenous RNA mechanism to modulate the host cell mitochondrial function and autophagy to facilitate parasite propagation. The findings suggest a novel immune evasion strategy of <i>N. caninum</i> to facilitate intracellular propagation and provide an alternative path to develop control strategies against neosporosis.