Bovine milk RNases modulate pro-inflammatory responses induced by nucleic acids in cultured immune and epithelial cells

Activation of innate immune receptors by exogenous substances is crucial for the detection of microbial pathogens and a subsequent inflammatory response. The inflammatory response to microbial lipopolysaccharide via Toll-like receptor 4 (TLR4) is facilitated by soluble accessory proteins, but the ro...

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Veröffentlicht in:Developmental and comparative immunology 2017-03, Vol.68, p.87-97
Hauptverfasser: Gupta, Sandeep K., Haigh, Brendan J., Seyfert, Hans-Martin, Griffin, Frank J., Wheeler, Thomas T.
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container_issue
container_start_page 87
container_title Developmental and comparative immunology
container_volume 68
creator Gupta, Sandeep K.
Haigh, Brendan J.
Seyfert, Hans-Martin
Griffin, Frank J.
Wheeler, Thomas T.
description Activation of innate immune receptors by exogenous substances is crucial for the detection of microbial pathogens and a subsequent inflammatory response. The inflammatory response to microbial lipopolysaccharide via Toll-like receptor 4 (TLR4) is facilitated by soluble accessory proteins, but the role of such proteins in the activation of other pathogen recognition receptors for microbial nucleic acid is not well understood. Here we demonstrate that RNase4 and RNase5 purified from bovine milk bind to Salmonella typhimurium DNA and stimulate pro-inflammatory responses induced by nucleic acid mimetics and S. typhimurium DNA in an established mouse macrophage cell culture model, RAW264.7, as well as in primary bovine mammary epithelial cells. RNase4 and 5 also modulated pro-inflammatory signalling in response to nucleic acids in bovine peripheral blood mononuclear cells, although producing a distinct response. These results support a role for RNase4 and RNase5 in mediating inflammatory signals in both immune and epithelial cells, involving mechanisms that are cell-type specific. •Milk RNase4 and 5 stimulate pro-inflammatory responses against nucleic acid mimetics.•Both RNases affect TLR3, TLR7 and TLR9 signalling in a mouse macrophage cell line.•These effects were also observed with natural DNA in bovine mammary epithelial cells.•The RNases showed distinct effects on the responses induced by natural DNA in bovine PBMCs.•The results suggest the RNases assist pathogen recognition in the mammary gland.
doi_str_mv 10.1016/j.dci.2016.11.015
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The inflammatory response to microbial lipopolysaccharide via Toll-like receptor 4 (TLR4) is facilitated by soluble accessory proteins, but the role of such proteins in the activation of other pathogen recognition receptors for microbial nucleic acid is not well understood. Here we demonstrate that RNase4 and RNase5 purified from bovine milk bind to Salmonella typhimurium DNA and stimulate pro-inflammatory responses induced by nucleic acid mimetics and S. typhimurium DNA in an established mouse macrophage cell culture model, RAW264.7, as well as in primary bovine mammary epithelial cells. RNase4 and 5 also modulated pro-inflammatory signalling in response to nucleic acids in bovine peripheral blood mononuclear cells, although producing a distinct response. 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The inflammatory response to microbial lipopolysaccharide via Toll-like receptor 4 (TLR4) is facilitated by soluble accessory proteins, but the role of such proteins in the activation of other pathogen recognition receptors for microbial nucleic acid is not well understood. Here we demonstrate that RNase4 and RNase5 purified from bovine milk bind to Salmonella typhimurium DNA and stimulate pro-inflammatory responses induced by nucleic acid mimetics and S. typhimurium DNA in an established mouse macrophage cell culture model, RAW264.7, as well as in primary bovine mammary epithelial cells. RNase4 and 5 also modulated pro-inflammatory signalling in response to nucleic acids in bovine peripheral blood mononuclear cells, although producing a distinct response. These results support a role for RNase4 and RNase5 in mediating inflammatory signals in both immune and epithelial cells, involving mechanisms that are cell-type specific. •Milk RNase4 and 5 stimulate pro-inflammatory responses against nucleic acid mimetics.•Both RNases affect TLR3, TLR7 and TLR9 signalling in a mouse macrophage cell line.•These effects were also observed with natural DNA in bovine mammary epithelial cells.•The RNases showed distinct effects on the responses induced by natural DNA in bovine PBMCs.•The results suggest the RNases assist pathogen recognition in the mammary gland.</description><subject>Activation</subject><subject>Animals</subject><subject>Bovine PBMCs</subject><subject>Cattle</subject><subject>Cell culture</subject><subject>Cow's milk</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Bacterial - immunology</subject><subject>Endoribonucleases - immunology</subject><subject>Endoribonucleases - metabolism</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - immunology</subject><subject>Female</subject><subject>Host defence</subject><subject>Immune modulation</subject><subject>Immune system</subject><subject>Immunology</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammatory response</subject><subject>Leukocytes (mononuclear)</subject><subject>Lipopolysaccharides</subject><subject>Macrophage</subject><subject>Macrophages</subject><subject>Macrophages - immunology</subject><subject>Mammary gland</subject><subject>Mammary Glands, Animal - pathology</subject><subject>Mastitis</subject><subject>Mice</subject><subject>Microorganisms</subject><subject>Milk</subject><subject>Milk - immunology</subject><subject>Milk - metabolism</subject><subject>Nucleic acids</subject><subject>Pathogens</subject><subject>Peripheral blood mononuclear cells</subject><subject>Proteins</subject><subject>RAW 264.7 Cells</subject><subject>Receptors</subject><subject>Ribonuclease, Pancreatic - immunology</subject><subject>Ribonuclease, Pancreatic - metabolism</subject><subject>RNase</subject><subject>Salmonella</subject><subject>Salmonella Infections - immunology</subject><subject>Salmonella typhimurium - genetics</subject><subject>Salmonella typhimurium - immunology</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><issn>0145-305X</issn><issn>1879-0089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-LFDEQxYMo7rj6AbxIwIuXblPp7kkaT-7iP1gURMFbSCfVmDGdjElnZb69aWb14MFcKlC_eryqR8hTYC0w2L88tNa4ltdvC9AyGO6RHUgxNozJ8T7ZMeiHpmPDtwvyKOcDq08Ce0guuJACZAc78usq3rqAdHH-B_38UWfMdIm2eL0iPabYuDB7vSx6jelEE-ZjDBvjgi0GLZ1ONBTj0RmqjbNbg5ri15Jq0y1Lqdo6WIpHt35H77SnBr3Pj8mDWfuMT-7qJfn69s2X6_fNzad3H65f3zSmk7A2VkiJsLdsHOehG_W-m2FCroe6LKDVQo_dLIzcz5J1GzjZsRK9EZIbPpnukrw469ZdfhbMq1pc3hzogLFkBbLnwyiBQ0Wf_4MeYkmhulOc8b6XnAtRKThTJsWcE87qmNyi00kBU1sq6qBqKmpLRQGoarTOPLtTLtOC9u_Enxgq8OoMYD3FrcOksnEY6oFdQrMqG91_5H8D9DOedQ</recordid><startdate>201703</startdate><enddate>201703</enddate><creator>Gupta, Sandeep K.</creator><creator>Haigh, Brendan J.</creator><creator>Seyfert, Hans-Martin</creator><creator>Griffin, Frank J.</creator><creator>Wheeler, Thomas T.</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201703</creationdate><title>Bovine milk RNases modulate pro-inflammatory responses induced by nucleic acids in cultured immune and epithelial cells</title><author>Gupta, Sandeep K. ; 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The inflammatory response to microbial lipopolysaccharide via Toll-like receptor 4 (TLR4) is facilitated by soluble accessory proteins, but the role of such proteins in the activation of other pathogen recognition receptors for microbial nucleic acid is not well understood. Here we demonstrate that RNase4 and RNase5 purified from bovine milk bind to Salmonella typhimurium DNA and stimulate pro-inflammatory responses induced by nucleic acid mimetics and S. typhimurium DNA in an established mouse macrophage cell culture model, RAW264.7, as well as in primary bovine mammary epithelial cells. RNase4 and 5 also modulated pro-inflammatory signalling in response to nucleic acids in bovine peripheral blood mononuclear cells, although producing a distinct response. These results support a role for RNase4 and RNase5 in mediating inflammatory signals in both immune and epithelial cells, involving mechanisms that are cell-type specific. •Milk RNase4 and 5 stimulate pro-inflammatory responses against nucleic acid mimetics.•Both RNases affect TLR3, TLR7 and TLR9 signalling in a mouse macrophage cell line.•These effects were also observed with natural DNA in bovine mammary epithelial cells.•The RNases showed distinct effects on the responses induced by natural DNA in bovine PBMCs.•The results suggest the RNases assist pathogen recognition in the mammary gland.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>27871831</pmid><doi>10.1016/j.dci.2016.11.015</doi><tpages>11</tpages></addata></record>
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subjects Activation
Animals
Bovine PBMCs
Cattle
Cell culture
Cow's milk
Deoxyribonucleic acid
DNA
DNA, Bacterial - immunology
Endoribonucleases - immunology
Endoribonucleases - metabolism
Epithelial cells
Epithelial Cells - immunology
Female
Host defence
Immune modulation
Immune system
Immunology
Immunomodulation
Inflammation
Inflammation - immunology
Inflammatory response
Leukocytes (mononuclear)
Lipopolysaccharides
Macrophage
Macrophages
Macrophages - immunology
Mammary gland
Mammary Glands, Animal - pathology
Mastitis
Mice
Microorganisms
Milk
Milk - immunology
Milk - metabolism
Nucleic acids
Pathogens
Peripheral blood mononuclear cells
Proteins
RAW 264.7 Cells
Receptors
Ribonuclease, Pancreatic - immunology
Ribonuclease, Pancreatic - metabolism
RNase
Salmonella
Salmonella Infections - immunology
Salmonella typhimurium - genetics
Salmonella typhimurium - immunology
Signal Transduction
Signaling
TLR4 protein
Toll-Like Receptor 4 - metabolism
Toll-like receptors
title Bovine milk RNases modulate pro-inflammatory responses induced by nucleic acids in cultured immune and epithelial cells
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