Skip to main content

Advertisement

Log in

A sentinel function for teat tissues in dairy cows: dominant innate immune response elements define early response to E. coli mastitis

  • Original Paper
  • Published:
Functional & Integrative Genomics Aims and scope Submit manuscript

Abstract

Escherichia coli intramammary infection elicits localized and systemic responses, some of which have been characterized in mammary secretory tissue. Our objective was to characterize gene expression patterns that become activated in different regions of the mammary gland during the acute phase of experimentally induced E. coli mastitis. Tissues evaluated were from Fürstenburg’s rosette, teat cistern (TC), gland cistern (GC), and lobulo-alveolar (LA) regions of control and infected mammary glands, 12 and 24 h after bacterial (or control) infusions. The main networks activated by E. coli infection pertained to immune and inflammatory response, with marked induction of genes encoding proteins that function in chemotaxis and leukocyte activation and signaling. Genomic response at 12 h post-infection was greatest in tissues of the TC and GC. Only at 24 h post-infection did tissue from the LA region respond, at which time the response was the greatest of all regions. Similar genetic networks were impacted in all regions during early phases of intramammary infection, although regional differences throughout the gland were noted. Data support an important sentinel function for the teat, as these tissues responded rapidly and intensely, with production of cytokines and antimicrobial peptides.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Alluwaimi AM (2004) The cytokines of bovine mammary gland: prospects for diagnosis and therapy. Res Vet Sci 77:211–222

    Article  PubMed  CAS  Google Scholar 

  • Bannerman DD (2009) Pathogen-dependent induction of cytokines and other soluble inflammatory mediators during intramammary infection of dairy cows. J Anim Sci 87:10–25

    Article  PubMed  CAS  Google Scholar 

  • Bannerman DD, Paape MJ, Hare WR, Sohn EJ (2003) Increased levels of LPS-binding protein in bovine blood and milk following bacterial lipopolysaccharide challenge. J Dairy Sci 86:3128–3137

    PubMed  CAS  Google Scholar 

  • Bannerman DD, Paape MJ, Lee JW, Zhao X, Hope JC, Rainard P (2004) Escherichia coli and Staphylococcus aureus elicit differential innate immune responses following intramammary infection. Clin Diagn Lab Immunol 11:463–472

    PubMed  Google Scholar 

  • Bannerman DD, Paape MJ, Chockalingam A (2006) Staphylococcus aureus intramammary infection elicits increased production of transforming growth factor-alpha, beta1, and beta2. Vet Immunol Immunopathol 112:309–315

    Article  PubMed  CAS  Google Scholar 

  • Bannerman DD, Rinaldi M, Vinyard BT, Laihia J, Leino L (2009) Effects of intramammary infusion of cis-urocanic acid on mastitis-associated inflammation and tissue injury in dairy cows. Am J Vet Res 70:373–382

    Article  PubMed  Google Scholar 

  • Barksby HE, Lea SR, Preshaw PM, Taylor JJ (2007) The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol 149:217–225

    Article  PubMed  CAS  Google Scholar 

  • Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193

    Article  PubMed  CAS  Google Scholar 

  • Bradley A (2002) Bovine mastitis: an evolving disease. Vet J 164:116–128

    Article  PubMed  CAS  Google Scholar 

  • Bruckmaier RM (2005) Gene expression of factors related to the immune reaction in response to intramammary Escherichia coli lipopolysaccharide challenge. J Dairy Res 72:120–124

    Article  PubMed  CAS  Google Scholar 

  • Burvenich C, Van Merris V, Mehrzad J, Diez-Fraile A, Duchateau L (2003) Severity of E. coli mastitis is mainly determined by cow factors. Vet Res 34:521–564

    Article  PubMed  Google Scholar 

  • Burvenich C, Bannerman DD, Lippolis JD, Peelman L, Nonnecke BJ, Kehrli ME Jr, Paape MJ (2007) Cumulative physiological events influence the inflammatory response of the bovine udder to Escherichia coli infections during the transition period. J Dairy Sci 90(Suppl 1):E39–54

    PubMed  Google Scholar 

  • Canny GO, Trifonova RT, Kindelberger DW, Colgan SP, Fichorova RN (2006) Expression and function of bactericidal/permeability-increasing protein in human genital tract epithelial cells. J Infect Dis 194:498–502

    Article  PubMed  CAS  Google Scholar 

  • Capuco AV, Bright SA, Pankey JW, Wood DL, Miller RH, Bitman J (1992) Increased susceptibility to intramammary infection following removal of teat canal keratin. J Dairy Sci 75:2126–2130

    PubMed  CAS  Google Scholar 

  • Cates EA, Connor EE, Mosser DM, Bannerman DD (2009) Functional characterization of bovine TIRAP and MyD88 in mediating bacterial lipopolysaccharide-induced endothelial NF-kappaB activation and apoptosis. Comp Immunol Microbiol Infect Dis 32:477–490

    Google Scholar 

  • Chockalingam A, Paape MJ, Bannerman DD (2005) Increased milk levels of transforming growth factor-alpha, beta1, and beta2 during Escherichia coli-induced mastitis. J Dairy Sci 88:1986–1993

    Article  PubMed  CAS  Google Scholar 

  • Chockalingam A, McKinney CE, Rinaldi M, Zarlenga DS, Bannerman DD (2007a) A peptide derived from human bactericidal/permeability-increasing protein (BPI) exerts bactericidal activity against Gram-negative bacterial isolates obtained from clinical cases of bovine mastitis. Vet Microbiol 125:80–90

    Article  PubMed  CAS  Google Scholar 

  • Chockalingam A, Zarlenga DS, Bannerman DD (2007b) Antimicrobial activity of bovine bactericidal permeability-increasing protein-derived peptides against gram-negative bacteria isolated from the milk of cows with clinical mastitis. Am J Vet Res 68:1151–1159

    Article  PubMed  CAS  Google Scholar 

  • Corl CM, Gandy JC, Sordillo LM (2008) Platelet activating factor production and proinflammatory gene expression in endotoxin-challenged bovine mammary endothelial cells. J Dairy Sci 91:3067–3078

    Article  PubMed  CAS  Google Scholar 

  • Derynck R (1992) The physiology of transforming growth factor-alpha. Adv Cancer Res 58:27–52

    Article  PubMed  CAS  Google Scholar 

  • Godson DL, Baca-Estrada ME, Van Kessel AG, Hughes HP, Morsy MA, Van Donkersgoed J, Harland RJ, Shuster DE, Daley MJ, Babiuk LA (1995) Regulation of bovine acute phase responses by recombinant interleukin-1 beta. Can J Vet Res 59:249–255

    PubMed  CAS  Google Scholar 

  • Griesbeck-Zilch B, Meyer HH, Kuhn CH, Schwerin M, Wellnitz O (2008) Staphylococcus aureus and Escherichia coli cause deviating expression profiles of cytokines and lactoferrin messenger ribonucleic acid in mammary epithelial cells. J Dairy Sci 91:2215–2224

    Article  PubMed  CAS  Google Scholar 

  • Harada A, Sekido N, Akahoshi T, Wada T, Mukaida N, Matsushima K (1994) Essential involvement of interleukin-8 (IL-8) in acute inflammation. J Leukoc Biol 56:559–564

    PubMed  CAS  Google Scholar 

  • Hogan J, Smith LK (2003) Coliform mastitis. Vet Res 34:507–519

    Article  PubMed  Google Scholar 

  • Hyde S (1999) Likelihood based inference on the Box–Cox family of transformations: SAS and Matlab programs. Dept of Mathematical Sciences, Montana State University, Billings 34p

    Google Scholar 

  • Ibeagha-Awemu EM, Lee JW, Ibeagha AE, Bannerman DD, Paape MJ, Zhao X (2008) Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells. Vet Res 39:11

    Article  PubMed  CAS  Google Scholar 

  • Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264

    Article  PubMed  Google Scholar 

  • Koj A (1996) Initiation of acute phase response and synthesis of cytokines. Biochim Biophys Acta 1317:84–94

    PubMed  Google Scholar 

  • Larson MA, Weber A, Weber AT, McDonald TL (2005) Differential expression and secretion of bovine serum amyloid A3 (SAA3) by mammary epithelial cells stimulated with prolactin or lipopolysaccharide. Vet Immunol Immunopathol 107:255–264

    Article  PubMed  CAS  Google Scholar 

  • Lee JW, Bannerman DD, Paape MJ, Huang MK, Zhao X (2006) Characterization of cytokine expression in milk somatic cells during intramammary infections with Escherichia coli or Staphylococcus aureus by real-time PCR. Vet Res 37:219–229

    Article  PubMed  CAS  Google Scholar 

  • Li RW, Li C (2006) Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells. BMC Genomics 7:234

    Article  PubMed  CAS  Google Scholar 

  • Logdberg L, Wester L (2000) Immunocalins: a lipocalin subfamily that modulates immune and inflammatory responses. Biochim Biophys Acta 1482:284–297

    PubMed  CAS  Google Scholar 

  • Long E, Capuco AV, Wood DL, Sonstegard T, Tomita G, Paape MJ, Zhao X (2001) Escherichia coli induces apoptosis and proliferation of mammary cells. Cell Death Differ 8:808–816

    Article  PubMed  CAS  Google Scholar 

  • Maeda H, Akaike T (1998) Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry (Mosc) 63:854–865

    CAS  Google Scholar 

  • Matsukawa A, Hogaboam CM, Lukacs NW, Kunkel SL (2000) Chemokines and innate immunity. Rev Immunogenet 2:339–358

    PubMed  CAS  Google Scholar 

  • McBride OW, Korn ED (1963) The lipoprotein lipase of mammary gland and the correlation of its activity to lactation. J Lipid Res 4:17–20

    PubMed  CAS  Google Scholar 

  • McClenahan D, Krueger R, Lee HY, Thomas C, Kehrli ME Jr, Czuprynski C (2006) Interleukin-8 expression by mammary gland endothelial and epithelial cells following experimental mastitis infection with E. coli. Comp Immunol Microbiol Infect Dis 29:127–137

    Article  PubMed  Google Scholar 

  • Menzies M, Ingham A (2006) Identification and expression of toll-like receptors 1–10 in selected bovine and ovine tissues. Vet Immunol Immunopathol 109:23–30

    Article  PubMed  CAS  Google Scholar 

  • Murphy MP (1999) Nitric oxide and cell death. Biochim Biophys Acta 1411:401–414

    Article  PubMed  CAS  Google Scholar 

  • Nickerson SC, Pankey JW (1983) Cytologic observations of the bovine teat end. Am J Vet Res 44:1433–1441

    PubMed  CAS  Google Scholar 

  • Nickerson SC, Pankey JW, Boddie NT (1984) Distribution, location, and ultrastructure of plasma cells in the uninfected, lactating bovine mammary gland. J Dairy Res 51:209–217

    Article  PubMed  CAS  Google Scholar 

  • Pannen BH, Robotham JL (1995) The acute-phase response. New Horiz 3:183–197

    PubMed  CAS  Google Scholar 

  • Pareek R, Wellnitz O, Van Dorp R, Burton J, Kerr D (2005) Immunorelevant gene expression in LPS-challenged bovine mammary epithelial cells. J Appl Genet 46:171–177

    PubMed  Google Scholar 

  • Petrovski KR, Trajcev M, Buneski G (2006) A review of the factors affecting the costs of bovine mastitis. J S Afr Vet Assoc 77:52–60

    PubMed  CAS  Google Scholar 

  • Petzl W, Zerbe H, Gunther J, Yang W, Seyfert HM, Nurnberg G, Schuberth HJ (2008) Escherichia coli, but not Staphylococcus aureus triggers an early increased expression of factors contributing to the innate immune defense in the udder of the cow. Vet Res 39:18

    Article  PubMed  CAS  Google Scholar 

  • Rainard P, Riollet C (2006) Innate immunity of the bovine mammary gland. Vet Res 37:369–400

    Article  PubMed  CAS  Google Scholar 

  • Riollet C, Rainard P, Poutrel B (2000) Differential induction of complement fragment C5a and inflammatory cytokines during intramammary infections with Escherichia coli and Staphylococcus aureus. Clin Diagn Lab Immunol 7:161–167

    PubMed  CAS  Google Scholar 

  • Shuster DE, Kehrli ME Jr, Rainard P, Paape M (1997) Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli. Infect Immun 65:3286–3292

    PubMed  CAS  Google Scholar 

  • Sohn EJ, Paape MJ, Bannerman DD, Connor EE, Fetterer RH, Peters RR (2007) Shedding of sCD14 by bovine neutrophils following activation with bacterial lipopolysaccharide results in down-regulation of IL-8. Vet Res 38:95–108

    Article  PubMed  CAS  Google Scholar 

  • Spits H, de Waal Malefyt R (1992) Functional characterization of human IL-10. Int Arch Allergy Immunol 99:8–15

    Article  PubMed  CAS  Google Scholar 

  • Storey JD, Tibshirani R (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 100:9440–9445

    Article  PubMed  CAS  Google Scholar 

  • Strandberg Y, Gray C, Vuocolo T, Donaldson L, Broadway M, Tellam R (2005) Lipopolysaccharide and lipoteichoic acid induce different innate immune responses in bovine mammary epithelial cells. Cytokine 31:72–86

    Article  PubMed  CAS  Google Scholar 

  • Suffredini AF, Fantuzzi G, Badolato R, Oppenheim JJ, O'Grady NP (1999) New insights into the biology of the acute phase response. J Clin Immunol 19:203–214

    Article  PubMed  CAS  Google Scholar 

  • Swanson KM, Stelwagen K, Dobson J, Henderson HV, Davis SR, Farr VC, Singh K (2009) Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model. J Dairy Sci 92:117–129

    Article  PubMed  CAS  Google Scholar 

  • Takeda K (2005) Evolution and integration of innate immune recognition systems: the Toll-like receptors. J Endotoxin Res 11:51–55

    PubMed  CAS  Google Scholar 

  • Thielen MA, Mielenz M, Hiss S, Zerbe H, Petzl W, Schuberth HJ, Seyfert HM, Sauerwein H (2007) Short communication: cellular localization of haptoglobin mRNA in the experimentally infected bovine mammary gland. J Dairy Sci 90:1215–1219

    Article  PubMed  CAS  Google Scholar 

  • Weiss J (2003) Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP): structure, function and regulation in host defence against Gram-negative bacteria. Biochem Soc Trans 31:785–790

    Article  PubMed  CAS  Google Scholar 

  • Werling D, Coffey TJ (2007) Pattern recognition receptors in companion and farm animals - the key to unlocking the door to animal disease? Vet J 174:240–251

    Article  PubMed  CAS  Google Scholar 

  • Yang W, Zerbe H, Petzl W, Brunner RM, Gunther J, Draing C, von Aulock S, Schuberth HJ, Seyfert HM (2008) Bovine TLR2 and TLR4 properly transduce signals from Staphylococcus aureus and E. coli, but S. aureus fails to both activate NF-kappaB in mammary epithelial cells and to quickly induce TNFalpha and interleukin-8 (CXCL8) expression in the udder. Mol Immunol 45:1385–1397

    Article  PubMed  CAS  Google Scholar 

  • Zeng R, Bequette BJ, Vinyard BT, Bannerman DD (2009) Determination of milk and blood concentrations of lipopolysaccharide-binding protein in cows with naturally acquired subclinical and clinical mastitis. J Dairy Sci 92:980–989

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the assistance of personnel of Research Animal Services, BARC. This research was funded by the United States Department of Agriculture, Agricultural Research Service, CRIS 1265-31000-083-00D, with participation by scientists at Ghent University made possible through FWO Vlaanderen, grant number G.0050.06N.

Disclaimer

Mention of trade names or commercial products in this publication is solely for providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anthony V. Capuco.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

Supplementary Table S1

Unique sequences (539 unique sequences including 152 annotated human orthologs) significantly regulated (FDR ≤ 10%) in at least one region of the bovine mammary gland during Escherichia coli infection. Numbers represent fold increase relative to control (PBS 24 h) = 1.0 (XLS 3881 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rinaldi, M., Li, R.W., Bannerman, D.D. et al. A sentinel function for teat tissues in dairy cows: dominant innate immune response elements define early response to E. coli mastitis. Funct Integr Genomics 10, 21–38 (2010). https://doi.org/10.1007/s10142-009-0133-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10142-009-0133-z

Keywords

Navigation