Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy
ABSTRACT Neospora caninum 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 N. caninum infection, no effective drugs and vaccines are currently available. Long non-cod...
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American Society for Microbiology
2025-02-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01580-24 |
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| author | Shan-Shan Zhao De-Liang Tao Jin-Ming Chen Ming-Yi Zhang Xin Yang Jun-Ke Song Qun Liu Guang-Hui Zhao |
| author_facet | Shan-Shan Zhao De-Liang Tao Jin-Ming Chen Ming-Yi Zhang Xin Yang Jun-Ke Song Qun Liu Guang-Hui Zhao |
| author_sort | Shan-Shan Zhao |
| collection | DOAJ |
| description | ABSTRACT Neospora caninum 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 N. caninum 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 N. caninum infection induced significantly aberrant expression of lncRNA profiles in caprine endometrial epithelial cells (EECs). In the present study, we found that N. caninum infection specifically suppressed the expression of a novel lncRNA, XR_001919077.1, and knockdown of XR_001919077.1 with small interfering RNA significantly promoted the propagation of N. caninum in caprine EECs. Rapid amplification of cDNA ends analysis generated six splice variants of XR_001919077.1, with lengths ranging from 592 to 694 nt. Transfection of the full length of each variant markedly inhibited the propagation of N. caninum in caprine EECs. Further study suggested that XR_001919077.1 acted as a sponge of Chi-miR-93-5p to promote the expression of sirt1, and the XR_001919077.1/Chi-miR-93-5p/sirt1 axis significantly delayed the in vitro growth of N. caninum in caprine EECs by regulating host cell mitochondrial function and autophagy. Our findings provide a novel insight to understand the interactions between N. caninum 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. Neospora caninum is one of the most common pathogens causing miscarriage in ruminants and is able to naturally inhabit the uterus, with N. caninum tissue cysts found in the endometrium. Recent advances in N. caninum research have revealed aberrant expression of long non-coding RNA (lncRNA) profiles in infected caprine endometrial epithelial cells. In the present study, N. caninum, but not Toxoplasma gondii, which has similar morphological and biological features to N. caninum, specifically suppresses the expression of a host lncRNA, XR_ 001919077.1, 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 N. caninum to facilitate intracellular propagation and provide an alternative path to develop control strategies against neosporosis. |
| format | Article |
| id | doaj-art-6ed84d4fead04732b86bb6c422b0090e |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj-art-6ed84d4fead04732b86bb6c422b0090e2025-02-04T14:03:41ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-02-0113210.1128/spectrum.01580-24Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagyShan-Shan Zhao0De-Liang Tao1Jin-Ming Chen2Ming-Yi Zhang3Xin Yang4Jun-Ke Song5Qun Liu6Guang-Hui Zhao7Department of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaDepartment of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaDepartment of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaDepartment of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaDepartment of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaDepartment of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaNational Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Parasitology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, ChinaABSTRACT Neospora caninum 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 N. caninum 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 N. caninum infection induced significantly aberrant expression of lncRNA profiles in caprine endometrial epithelial cells (EECs). In the present study, we found that N. caninum infection specifically suppressed the expression of a novel lncRNA, XR_001919077.1, and knockdown of XR_001919077.1 with small interfering RNA significantly promoted the propagation of N. caninum in caprine EECs. Rapid amplification of cDNA ends analysis generated six splice variants of XR_001919077.1, with lengths ranging from 592 to 694 nt. Transfection of the full length of each variant markedly inhibited the propagation of N. caninum in caprine EECs. Further study suggested that XR_001919077.1 acted as a sponge of Chi-miR-93-5p to promote the expression of sirt1, and the XR_001919077.1/Chi-miR-93-5p/sirt1 axis significantly delayed the in vitro growth of N. caninum in caprine EECs by regulating host cell mitochondrial function and autophagy. Our findings provide a novel insight to understand the interactions between N. caninum 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. Neospora caninum is one of the most common pathogens causing miscarriage in ruminants and is able to naturally inhabit the uterus, with N. caninum tissue cysts found in the endometrium. Recent advances in N. caninum research have revealed aberrant expression of long non-coding RNA (lncRNA) profiles in infected caprine endometrial epithelial cells. In the present study, N. caninum, but not Toxoplasma gondii, which has similar morphological and biological features to N. caninum, specifically suppresses the expression of a host lncRNA, XR_ 001919077.1, 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 N. caninum to facilitate intracellular propagation and provide an alternative path to develop control strategies against neosporosis.https://journals.asm.org/doi/10.1128/spectrum.01580-24Neospora caninumXR_001919077.1propagationmitochondrial functionautophagy |
| spellingShingle | Shan-Shan Zhao De-Liang Tao Jin-Ming Chen Ming-Yi Zhang Xin Yang Jun-Ke Song Qun Liu Guang-Hui Zhao Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy Microbiology Spectrum Neospora caninum XR_001919077.1 propagation mitochondrial function autophagy |
| title | Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy |
| title_full | Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy |
| title_fullStr | Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy |
| title_full_unstemmed | Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy |
| title_short | Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy |
| title_sort | neospora caninum infection specifically suppresses the expression of a host lncrna xr 001919077 1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy |
| topic | Neospora caninum XR_001919077.1 propagation mitochondrial function autophagy |
| url | https://journals.asm.org/doi/10.1128/spectrum.01580-24 |
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