Abstract
Bovine herpesvirus-4 (BoHV-4) and bovine viral diarrhea virus (BVDV) infect the uterus of cattle, often resulting in reduced fertility, or abortion of the fetus, respectively. Here, exposure of primary bovine endometrial cells to BoHV-4 or BVDV modulated the production of inflammatory mediators. Viral pathogen-associated molecular patterns (PAMPs) are detected via pattern-recognition receptors (PRRs). However, the relative contribution of specific PRRs to innate immunity, during viral infection of the uterus, is unclear. Endometrial epithelial and stromal cells constitutively express the PRR Toll-like receptor (TLR)-3, but, the status of retinoic acid-inducible gene I (RIG-I), a sensor of cytosolic nucleic acids, is unknown. Primary endometrial epithelial and stromal cells had low expression of RIG-I, which was increased in stromal cells after 12 h transfection with the TLR3 ligand Poly(I:C), a synthetic analog of double-stranded RNA. Furthermore, short interfering RNA targeting TLR3, or interferon (IFN) regulatory transcription factor 3, an inducer of type I IFN transcription, reduced Poly(I:C)-induced RIG-I protein expression and reduced inflammatory mediator secretion from stromal cells. We conclude that antiviral defense of endometrial stromal cells requires coordinated recognition of PAMPs, initially via TLR3 and later via inducible RIG-I.
Highlights
The initiation of the innate immune response to viruses depends on the detection of pathogenassociated molecular patterns (PAMPs) by pattern-recognition receptors (PRRs) [1]
In order to understand the recognition of viruses by endometrial epithelial and stromal cells and the induction of pro-inflammatory mediators and IFNs, we investigated the role of TLR3 and retinoic acid-inducible gene I (RIG-I) in the innate immune response to viable Bovine herpesvirus-4 (BoHV-4) and bovine viral diarrhea virus (BVDV), and viral pathogen-associated molecular patterns (PAMPs)
To characterize the innate immune response of the endometrium to viruses, endometrial ex vivo organ cultures (EVOCs), endometrial epithelial cells, and endometrial stromal cells were exposed to BoHV-4 or BVDV virus for 24 or 72 h
Summary
The initiation of the innate immune response to viruses depends on the detection of pathogenassociated molecular patterns (PAMPs) by pattern-recognition receptors (PRRs) [1]. The main families of PRRs are the Toll-like receptors (TLRs), nucleotide oligomerization domain-like receptors, retinoic acid-inducible gene I (RIG-I)-like receptors, and C-type lectin receptors. These receptors are most often expressed by hematopoietic cells, but the epithelial and stromal cells of the endometrium possess functional PRRs. The PRRs that detect uterine bacteria that contaminate the uterus, causing infertility, are well documented in cattle [2,3,4,5,6,7,8,9].
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