Toll-like receptor and antimicrobial peptide expression in the bovine endometrium

Davies, D. E.; Meade, Kieran G.; Herath, Shan; Eckersall, P.D.; González, Deyarina; White, John O.; Conlan, R. Steven; O’Farrelly, Cliona; Sheldon, I. Martin

doi:10.1186/1477-7827-6-53

Cited by 166 publications

(177 citation statements)

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“…In addition, ex vivo organ cultures of bovine endometrium accumulate IL1b, IL6, IL8, and prostaglandin E 2 when challenged with E. coli or T. pyogenes (Borges et al 2012, Amos et al 2014. Furthermore, pure populations of endometrial epithelial and stromal cells express most TLRs and their coreceptors, such as MD2 and CD14 (Herath et al 2006, Davies et al 2008. Addition of LPS to epithelial or stromal cells in vitro stimulates phosphorylation of MAPK and the nuclear translocation of NFkB, secretion of prostaglandin F 2a , prostaglandin E 2 , IL6 and IL8, and increased expression of antimicrobial peptides MUC1, LAP and TAP (Herath et al 2006, Davies et al 2008, Cronin et al 2012.…”

Section: R45mentioning

confidence: 99%

“…Furthermore, pure populations of endometrial epithelial and stromal cells express most TLRs and their coreceptors, such as MD2 and CD14 (Herath et al 2006, Davies et al 2008. Addition of LPS to epithelial or stromal cells in vitro stimulates phosphorylation of MAPK and the nuclear translocation of NFkB, secretion of prostaglandin F 2a , prostaglandin E 2 , IL6 and IL8, and increased expression of antimicrobial peptides MUC1, LAP and TAP (Herath et al 2006, Davies et al 2008, Cronin et al 2012. Intriguingly, the release of IL8 from polarised epithelial cells is vectorial and directed apically if the challenge is in the uterine lumen (MacKintosh et al 2013).…”

Section: R45mentioning

confidence: 99%

“…Antimicrobial peptides and mucosal glycoproteins also cover the mucosa to neutralise bacteria and prevent them reaching the epithelium. The principal cysteine-rich, cationic, antimicrobial peptides expressed in the bovine endometrium include b-defensins, lingual antimicrobial peptide (LAP), and tracheal antimicrobial peptide (TAP), and their transcripts are more abundant in the face of microbial challenge (Davies et al 2008, Chapwanya et al 2013. Other surface molecules that may help to protect the endometrium include the mucins; evidence for their role includes genetic deletion of Muc1 in mice, which is associated with chronic inflammation of the lower female reproductive tract by opportunistic bacterial infections (DeSouza et al 1999).…”

Section: Innate Immunitymentioning

confidence: 99%

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Innate immunity and inflammation of the bovine female reproductive tract in health and disease

Sheldon¹,

Cronin²,

Healey³

et al. 2014

Reproduction

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127

100

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Mammalian reproductive physiology and the development of viviparity co-evolved with inflammation and immunity over millennia. Many inflammatory mediators contribute to paracrine and endocrine signalling, and the maintenance of tissue homeostasis in the female reproductive tract. However, inflammation is also a feature of microbial infections of the reproductive tract. Bacteria and viruses commonly cause endometritis, perturb ovarian follicle development and suppress the endocrine activity of the hypothalamus and pituitary in cattle. Innate immunity is an evolutionary ancient system that orchestrates host cell inflammatory responses aimed at eliminating pathogens and repairing damaged tissue. Pattern recognition receptors on host cells bind pathogen-associated molecular patterns and damage-associated molecular patterns, leading to the activation of intracellular MAPK and NFkB signalling pathways and the release of inflammatory mediators. Inflammatory mediators typically include the interleukin cytokines IL1b and IL6, chemokines such as IL8, interferons and prostaglandins. This review outlines the mechanisms of inflammation and innate immunity in the bovine female reproductive tract during health and disease condition.

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Section: R45mentioning

confidence: 99%

Section: R45mentioning

confidence: 99%

Section: Innate Immunitymentioning

confidence: 99%

See 1 more Smart Citation

Innate immunity and inflammation of the bovine female reproductive tract in health and disease

Sheldon¹,

Cronin²,

Healey³

et al. 2014

Reproduction

Self Cite

127

100

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“…Despite evidence for their involvement in uterine biology of humans and mice, there is a lack of information regarding the role of TLR-mediated pathways in ruminants. Reports on expression of TLR1-TLR10 in bovine endometria describe differences in expression between epithelial and stromal cells (Herath et al 2006, Davies et al 2008 and their abundance in uterine endometrium of goats (Tirumurugaan et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Ruiz-Gonzalez¹,

Minten²,

Wang³

et al. 2015

Reproduction

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Toll-like receptors (TLRs) belong to the innate immune system and regulate inflammatory events that affect mammalian reproduction.In Study 1, we demonstrated that abundance of ovine TLR1-TLR9 mRNAs in the uterus differs due to reproductive status (TLR2, TLR3, TLR7, and TLR8) and the day of the estrous cycle and pregnancy (TLR1-TLR3, TLR5-TLR7, and TLR9). Expression of TLR7 and TLR8 proteins was localized primarily to uterine epithelia and stroma and regulated in a temporal manner. In Study 2, we determined that ovine conceptuses express TLR7 and TLR8 on all days studied and that expression of the envelope protein of ovine endogenous retrovirus (enJSRV-Env) declined in conceptus trophectoderm from Day 13 to Day 16 of pregnancy. In Study 3, loss-of-function experiments were conducted in vivo using morpholino antisense oligonucleotides (MAOs) injected into the uterine lumen to block synthesis of TLR7 and TLR8 proteins, individually and jointly. Conceptuses were recovered on Day 16 to assess their morphology. MAO-treated conceptuses were developmentally retarded, produced less interferon tau (IFNT), and had fewer binucleate cells (BNCs) compared with MAO-Controls. Moreover, expression of enJSRV-Env mRNA in MAO-TLR7 conceptuses was greater than that for MAO-Control and MAO-TLR8 conceptuses, but similar to MAO-TLR7/TLR8 conceptuses. Results of this study indicated differences in TLR1-TLR9 expression due to reproductive status and the day of the estrous cycle and pregnancy. TLR7 and TLR8 also influence development, enJSRV-Env abundance, secretion of IFNT, and formation of BNCs by conceptuses. These findings corroborate our hypothesis that TLR7 and TLR8 mediate pathways whereby enJSRV-Env regulates key peri-implantation events in conceptus development and differentiated functions of trophectoderm cells.

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“…These cells express PRRs such as TLRs [18] and are able to mount an innate immune response to bacteria [19] or bacterial ligands such as LPS [20] [21].…”

Section: Introductionmentioning

confidence: 99%

Bovine Endometrial Cells Mount Innate Immune Response to the Intracellular Ligands CL097 and Poly(dA:dT) Indicating Roles against Uterine Viruses

Oguejiofor¹,

Cheng²,

Fouladi-Nashta³

et al. 2017

OJAS

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Uterine infection and endometritis cause infertility and economic losses in the cattle industry. The innate immune response of the endometrium is critical in the elimination of pathogenic organisms that invade the uterus in postpartum cows. This study investigated the response of bovine endometrium to synthetic intracellular ligands which activate innate immunity by stimulating similar receptors to those used to recognise the presence of some viruses. Mixed primary epithelial and stromal cell cultures were treated with 5 μg/ml of CL097 (a TLR7/8 ligand) or 2 μg/ml of poly(dA:dT) (a DNA analogue) for either 6 h or 24 h. Cellular responses were assessed by the mRNA expression of 18 immune-related genes and 3 endogenous reference genes by conventional PCR followed by qRT-PCR from four replicate experiments. Bovine endometrial cells expressed the cytosolic pattern recognition receptors (PRRs) DDX58 (RIG-I), IFIH1 (MDA5) and LRRFIP1 which act as intracellular nucleic acid sensors. Neither ligand altered the expression of the extra-cytosolic pattern recognition receptors (PRRs) TLR3, TLR4, TLR7 or TLR8 whereas poly(dA:dT) treatment increased the expression of IFIH1 and DDX58.

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Toll-like receptor and antimicrobial peptide expression in the bovine endometrium

Cited by 166 publications

References 45 publications

Innate immunity and inflammation of the bovine female reproductive tract in health and disease

Innate immunity and inflammation of the bovine female reproductive tract in health and disease

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Bovine Endometrial Cells Mount Innate Immune Response to the Intracellular Ligands CL097 and Poly(dA:dT) Indicating Roles against Uterine Viruses

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