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 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 infection induced significantly aberrant expression of lncRNA profiles in caprine endometrial epithelial cells (EECs). In the present study, we found that infection specifically suppressed the expression of a novel lncRNA, , and knockdown of with small interfering RNA significantly promoted the propagation of in caprine EECs. Rapid amplification of cDNA ends analysis generated six splice variants of , with lengths ranging from 592 to 694 nt. Transfection of the full length of each variant markedly inhibited the propagation of in caprine EECs. Further study suggested that acted as a sponge of Chi-miR-93-5p to promote the expression of , and the /Chi-miR-93-5p/ axis significantly delayed the growth of in caprine EECs by regulating host cell mitochondrial function and autophagy. Our findings provide a novel insight to understand the interactions between 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. is one of the most common pathogens causing miscarriage in ruminants and is able to naturally inhabit the uterus, with tissue cysts found in the endometrium. Recent advances in research have revealed aberrant expression of long non-coding RNA (lncRNA) profiles in infected caprine endometrial epithelial cells. In the present study, , but not which has similar morphological and biological features to , specifically suppresses the expression of a host lncRNA, , 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 to facilitate intracellular propagation and provide an alternative path to develop control strategies against neosporosis.
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http://dx.doi.org/10.1128/spectrum.01580-24 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen 52074, Germany.
Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
Host plants and various fungicides inhibit plant pathogens by inducing the release of excessive reactive oxygen species (ROS) and causing DNA damage, either directly or indirectly leading to cell death. The mechanisms by which the oomycete manages ROS stress resulting from plant immune responses and fungicides remains unclear. This study elucidates the role of histone acetylation in ROS-induced DNA damage responses (DDR) to adapt to stress.
View Article and Find Full Text PDFJ Proteome Res
January 2025
School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201, United States.
() utilizes heme as an iron source from the host during infection. Biliverdin beta and delta (BVIXβ and BVIXδ) are generated by HemO, specific to , while biliverdin alpha is generated from the bacterial BphO system and by mammalian heme oxygenases. Here, we have developed and characterized a quantitative LC-MS/MS assay for the separation of three endogenous isomers, BVIXα, BVIXβ, and BVIXδ.
View Article and Find Full Text PDFBlood
January 2025
Stanford University Medical Center, Stanford, California, United States.
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607).
View Article and Find Full Text PDFPLoS Pathog
January 2025
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection.
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