title: Comparison of the pathogen species-specific immune response in udder derived cell types and their models.
abstract: The outcome of an udder infection (mastitis) largely depends on the species of the invading pathogen. Gram-negative pathogens, such as Escherichia coli often elicit acute clinical mastitis while Gram-positive pathogens, such as Staphylococcus aureus tend to cause milder subclinical inflammations. It is unclear which type of the immune competent cells residing in the udder governs the pathogen species-specific physiology of mastitis and which established cell lines might provide suitable models. We therefore profiled the pathogen species-specific immune response of different cell types derived from udder and blood. Primary cultures of bovine mammary epithelial cells (pbMEC), mammary derived fibroblasts (pbMFC), and bovine monocyte-derived macrophages (boMdM) were challenged with heat-killed E. coli, S. aureus and S. uberis mastitis pathogens and their immune response was scaled against the response of established models for MEC (bovine MAC-T) and macrophages (murine RAW 264.7). Only E. coli provoked a full scale immune reaction in pbMEC, fibroblasts and MAC-T cells, as indicated by induced cytokine and chemokine expression and NF-κB activation. Weak reactions were induced by S. aureus and none by S. uberis challenges. In contrast, both models for macrophages (boMdM and RAW 264.7) reacted strongly against all the three pathogens accompanied by strong activation of NF-κB factors. Hence, the established cell models MAC-T and RAW 264.7 properly reflected key aspects of the pathogen species-specific immune response of the respective parental cell type. Our data imply that the pathogen species-specific physiology of mastitis likely relates to the respective response of MEC rather to that of professional immune cells.
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany. j.guenther@fbn-dummerstorf.de.
authors.forename: Juliane
authors.initials: J
authors.lastname: Günther
authors.affiliation: Immunology Unit, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany. mirja.koy@tiho-hannover.de.
authors.forename: Mirja
authors.initials: M
authors.lastname: Koy
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany. berthold@fbn-dummerstorf.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Berthold
authors.affiliation: Immunology Unit, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173, Hannover, Germany. hans-joachim.schubert@tiho-hannover.de.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schuberth
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany. seyfert@fbn-dummerstorf.de.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Seyfert
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008321:Mammary Glands, Animal / Q000276:immunology* / Q000382:microbiology; D008414:Mastitis, Bovine / Q000276:immunology* / Q000382:microbiology; D013045:Species Specificity; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D013211:Staphylococcus aureus / Q000276:immunology; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D013291:Streptococcus / Q000276:immunology
references.citation: J Dairy Sci. 2012 Jul;95(7):3852-64
references.pmid: 22720940
references.citation: J Dairy Sci. 2009 Jan;92(1):117-29
references.pmid: 19109270
references.citation: Mol Immunol. 2008 Mar;45(5):1385-97
references.pmid: 17936907
references.citation: Immunity. 2013 Dec 12;39(6):1003-18
references.pmid: 24332029
references.citation: BMC Genomics. 2010;11:138
references.pmid: 20184744
references.citation: Vet Res. 2003 Sep-Oct;34(5):521-64
references.pmid: 14556694
references.citation: Am J Reprod Immunol. 2015 Jun;73(6):487-500
references.pmid: 25269386
references.citation: J Biol Chem. 2015 May 22;290(21):13440-53
references.pmid: 25837248
references.citation: J Dairy Sci. 1996 Jun;79(6):1021-6
references.pmid: 8827466
references.citation: Handb Exp Pharmacol. 2008;(183):1-20
references.pmid: 18071652
references.citation: Cytokine. 2005 Jul 7;31(1):72-86
references.pmid: 15882946
references.citation: J Biol Chem. 1994 Oct 21;269(42):26431-7
references.pmid: 7523407
references.citation: J Leukoc Biol. 2003 Sep;74(3):448-55
references.pmid: 12949249
references.citation: Cytokine Growth Factor Rev. 2003 Oct;14(5):409-26
references.pmid: 12948524
references.citation: Front Immunol. 2012 Oct 29;3:322
references.pmid: 23112799
references.citation: Cell Mol Life Sci. 2015 Nov;72(21):4111-26
references.pmid: 26210152
references.citation: BMC Genomics. 2009;10:542
references.pmid: 19925655
references.citation: J Dairy Sci. 2004 Aug;87(8):2420-32
references.pmid: 15328264
references.citation: Cell. 2010 Mar 19;140(6):805-20
references.pmid: 20303872
references.citation: Innate Immun. 2012 Dec;18(6):886-96
references.pmid: 22627785
references.citation: Annu Rev Immunol. 2014;32:659-702
references.pmid: 24655300
references.citation: Vet Res. 2008 Mar-Apr;39(2):18
references.pmid: 18258172
references.citation: Mol Immunol. 2006 Feb;43(3):210-25
references.pmid: 16199258
references.citation: Vet Res. 2016;47:13
references.pmid: 26738804
references.citation: Expert Opin Ther Targets. 2013 Dec;17(12):1439-60
references.pmid: 24090198
references.citation: Trends Immunol. 2012 Nov;33(11):571-7
references.pmid: 22883707
references.citation: Nat Rev Immunol. 2005 Dec;5(12):953-64
references.pmid: 16322748
references.citation: J Leukoc Biol. 2013 Sep;94(3):449-58
references.pmid: 23787127
references.citation: Nat Protoc. 2010 Feb;5(2):303-22
references.pmid: 20134430
references.citation: Nat Rev Immunol. 2003 Sep;3(9):710-20
references.pmid: 12949495
references.citation: Cancer Lett. 2013 Jan 28;328(2):222-5
references.pmid: 23085193
references.citation: Vet Immunol Immunopathol. 2013 Oct 1;155(4):245-52
references.pmid: 24018311
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: J Leukoc Biol. 2009 Sep;86(3):529-43
references.pmid: 19564575
references.citation: Int Immunopharmacol. 2014 Jul;21(1):231-40
references.pmid: 24836680
references.citation: BMC Genomics. 2013;14:36
references.pmid: 23324411
references.citation: Cytokine Growth Factor Rev. 2015 Oct;26(5):475-87
references.pmid: 26189695
references.citation: J Dairy Sci. 2015 Mar;98(3):1836-50
references.pmid: 25597966
references.citation: Comp Immunol Microbiol Infect Dis. 2011 Jul;34(4):347-54
references.pmid: 21600652
references.citation: J Dairy Sci. 2001 Oct;84(10):2177-87
references.pmid: 11699449
references.citation: BMC Vet Res. 2008;4:18
references.pmid: 18513449
references.citation: Biochim Biophys Acta. 2011 May;1813(5):878-88
references.pmid: 21296109
references.citation: Infect Immun. 2004 Dec;72(12):7311-4
references.pmid: 15557657
references.citation: Cell Mol Life Sci. 2010 Sep;67(17):2909-35
references.pmid: 20454917
references.citation: J Dairy Sci. 2013 Jun;96(6):3723-36
references.pmid: 23587380
references.citation: Vet Res. 2009 Jul-Aug;40(4):31
references.pmid: 19321125
references.citation: J Mammary Gland Biol Neoplasia. 2011 Dec;16(4):357-72
references.pmid: 21968538
references.citation: J Immunol. 1977 Dec;119(6):2060-6
references.pmid: 915291
references.citation: Arthritis Rheum. 2010 Aug;62(8):2249-61
references.pmid: 20506350
references.citation: Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d
references.pmid: 21890489
references.citation: Mol Cancer. 2013;12:86
references.pmid: 23915189
references.citation: Clin Diagn Lab Immunol. 2004 Jan;11(1):174-85
references.pmid: 14715566
references.citation: J Anim Sci. 2009 Apr;87(13 Suppl):10-25
references.pmid: 18708595
references.citation: Mol Immunol. 2011 Mar;48(6-7):895-908
references.pmid: 21255844
references.citation: Vet Immunol Immunopathol. 2010 May 15;135(1-2):152-7
references.pmid: 19963279
references.citation: Nat Immunol. 2002 Mar;3(3):221-7
references.pmid: 11875461
references.citation: Cell. 1978 Sep;15(1):261-7
references.pmid: 212198
references.citation: Annu Rev Microbiol. 2014;68:439-58
references.pmid: 25002085
references.citation: Infect Immun. 2011 Feb;79(2):695-707
references.pmid: 21115717
references.citation: Genet Sel Evol. 2011;43:24
references.pmid: 21702919
references.citation: BMC Genomics. 2013;14:891
references.pmid: 24341851
references.citation: J Immunol. 2008 Jul 15;181(2):1245-54
references.pmid: 18606678
references.citation: Proc Natl Acad Sci U S A. 2012 May 8;109(19):7421-6
references.pmid: 22532668
references.citation: Clin Diagn Lab Immunol. 2004 May;11(3):463-72
references.pmid: 15138171
references.citation: Vet Immunol Immunopathol. 2011 Dec 15;144(3-4):270-89
references.pmid: 21955443
references.citation: BMC Vet Res. 2015;11:172
references.pmid: 26219462
references.citation: Infect Immun. 1994 Dec;62(12):5641-6
references.pmid: 7960146
references.citation: Exp Cell Res. 1991 Dec;197(2):191-9
references.pmid: 1659986