Journal of Mammary Gland Biology and Neoplasia

, Volume 16, Issue 4, pp 305–322 | Cite as

Functional Adaptations of the Transcriptome to Mastitis-Causing Pathogens: The Mammary Gland and Beyond

Article

Abstract

Application of microarrays to the study of intramammary infections in recent years has provided a wealth of fundamental information on the transcriptomics adaptation of tissue/cells to the disease. Due to its heavy toll on productivity and health of the animal, in vivo and in vitro transcriptomics works involving different mastitis-causing pathogens have been conducted on the mammary gland, primarily on livestock species such as cow and sheep, with few studies in non-ruminants. However, the response to an infectious challenge originating in the mammary gland elicits systemic responses in the animal and encompasses tissues such as liver and immune cells in the circulation, with also potential effects on other tissues such as adipose. The susceptibility of the animal to develop mastitis likely is affected by factors beyond the mammary gland, e.g. negative energy balance as it occurs around parturition. Objectives of this review are to discuss the use of systems biology concepts for the holistic study of animal responses to intramammary infection; providing an update of recent work using transcriptomics to study mammary and peripheral tissue (i.e. liver) as well as neutrophils and macrophage responses to mastitis-causing pathogens; discuss the effect of negative energy balance on mastitis predisposition; and analyze the bovine and murine mammary innate-immune responses during lactation and involution using a novel functional analysis approach to uncover potential predisposing factors to mastitis throughout an animal’s productive life.

Keywords

Systems biology Bioinformatics Transcriptomics Liver Ruminant 

Abbreviations

PMN

polymorphonuclear leukocytes

IMI

intramammary infection

ORA

overrepresented approach

FDR

false discovery rate

IPA

ingenuity pathway analysis

DIA

dynamic impact approach

E. coli

Escherichia coli

APR

acute-phase response

CXCL5

C-X-C motif chemokine 5

DEG

differentially expressed genes

S. epidermis

streptococcus epidermis

S. aureus

staphylococcus aureus

IL6

interleukin 6

NFKB2

NF-Kappa-B p100 subunit

S. uberis

streptococcus uberis

XBP1

X-box binding protein 1

SREBF1

sterol-regulatory element binding factor 1

PPAR

peroxisome proliferator activated receptor

PAMP

pathogen-associated molecular patterns

LPS

lipopolysacharide

LTA

lipoteichoic acid

NO

nitric oxide

SCC

somatic cell count

NET

neutrophil extracellular traps

GCP2

granulocyte chemotactic protein 2

C5a

complement 5a

pi

post-inoculation

NEFA

non-esterified fatty acids

NEB

negative energy balance

BHBA

hydroxybutyric acid

MHC

major histocompatibility complex

XDH

xanthine dehydrogenase

SPP1

osteopontin

MUC1

mucin 1

SNP

single nucleotide polymorphism

References

  1. 1.
    Rinaldi M, Li RW, Capuco AV. Mastitis associated transcriptomic disruptions in cattle. Vet Immunol Immunopathol. 2010;138(4):267–79.PubMedGoogle Scholar
  2. 2.
    Loor JJ, Cohick WS. ASAS centennial paper: lactation biology for the twenty-first century. J Anim Sci. 2009;87(2):813–24.PubMedGoogle Scholar
  3. 3.
    Bruggeman FJ, Westerhoff HV. The nature of systems biology. Trends Microbiol. 2007;15(1):45–50.PubMedGoogle Scholar
  4. 4.
    Cornish-Bowden A, Cardenas ML, Letelier JC, et al. Understanding the parts in terms of the whole. Biol Cell. 2004;96(9):713–7.PubMedGoogle Scholar
  5. 5.
    Wheeler MB, Monaco E, Bionaz M, et al. The role of existing and emerging biotechnologies for livestock production: toward holism. Acta Scientiae Veterinariae. 2010;s463–s84.Google Scholar
  6. 6.
    Greene CS, Troyanskaya OG. Integrative systems biology for data-driven knowledge discovery. Semin Nephrol. 2010;30(5):443–54.PubMedGoogle Scholar
  7. 7.
    Feist AM, Palsson BO. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat Biotechnol. 2008;26(6):659–67.PubMedGoogle Scholar
  8. 8.
    Germain RN, Meier-Schellersheim M, Nita-Lazar A, et al. Systems biology in immunology: a computational modeling perspective. Annu Rev Immunol. 2011;29:527–85.PubMedGoogle Scholar
  9. 9.
    Piantoni P, Bionaz M, Graugnard DE, et al. Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development. BMC Genomics. 2010;11:331.PubMedGoogle Scholar
  10. 10.
    da Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13.Google Scholar
  11. 11.
    Draghici S, Khatri P, Tarca AL, et al. A systems biology approach for pathway level analysis. Genome Res. 2007;17(10):1537–45.PubMedGoogle Scholar
  12. 12.
    Bionaz M, Periasamy K, Rodriguez-Zas S, et al. The bovine mammary transcriptome: a novel dynamics impact approach to uncover functional adaptations of the mammary gland during the lactation cycle. PLoS One. 2011 (Submitted).Google Scholar
  13. 13.
    da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57.Google Scholar
  14. 14.
    Buitenhuis B, Rontved CM, Edwards SM, et al. In depth analysis of genes and pathways of the mammary gland involved in the pathogenesis of bovine Escherichia coli-mastitis. BMC Genomics. 2011;12:130.PubMedGoogle Scholar
  15. 15.
    Rinaldi M, Li RW, Bannerman DD, 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. 2010;10(1):21–38.PubMedGoogle Scholar
  16. 16.
    Mitterhuemer S, Petzl W, Krebs S, et al. Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland. BMC Genomics. 2010;11:138.PubMedGoogle Scholar
  17. 17.
    Bonnefont CM, Toufeer M, Caubet C, et al. Transcriptomic analysis of milk somatic cells in mastitis resistant and susceptible sheep upon challenge with Staphylococcus epidermidis and Staphylococcus aureus. BMC Genomics. 2011;12:208.PubMedGoogle Scholar
  18. 18.
    Brand B, Hartmann A, Repsilber D, et al. Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score. Genet Sel Evol. 2011;43(1):24.PubMedGoogle Scholar
  19. 19.
    Vorbach C, Capecchi MR, Penninger JM. Evolution of the mammary gland from the innate immune system? Bioessays. 2006;28(6):606–16.PubMedGoogle Scholar
  20. 20.
    Genini S, Badaoui B, Sclep G, et al. Strengthening insights into host responses to mastitis infection in ruminants by combining heterogeneous microarray data sources. BMC Genomics. 2011;12(1):225.PubMedGoogle Scholar
  21. 21.
    Fierro AC, Vandenbussche F, Engelen K, et al. Meta analysis of gene expression data within and across species. Curr Genomics. 2008;9(8):525–34.PubMedGoogle Scholar
  22. 22.
    Huang Q, Liu D, Majewski P, et al. The plasticity of dendritic cell responses to pathogens and their components. Science. 2001;294(5543):870–5.PubMedGoogle Scholar
  23. 23.
    Nau GJ, Richmond JF, Schlesinger A, et al. Human macrophage activation programs induced by bacterial pathogens. Proc Natl Acad Sci USA. 2002;99(3):1503–8.PubMedGoogle Scholar
  24. 24.
    Moyes KM, Drackley JK, Morin DE, et al. Mammary gene expression profiles during an intramammary challenge reveal potential mechanisms linking negative energy balance with impaired immune response. Physiol Genomics. 2010.Google Scholar
  25. 25.
    Moyes KM, Drackley JK, Morin DE, et al. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARgamma signaling as potential mechanism for the negative relationships between immune response and lipid metabolism. BMC Genomics. 2009;10:542.PubMedGoogle Scholar
  26. 26.
    Petzl W, Zerbe H, Gunther J, et al. 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. 2008;39(2):18.PubMedGoogle Scholar
  27. 27.
    Burvenich C, Van Merris V, Mehrzad J, et al. Severity of E. coli mastitis is mainly determined by cow factors. Vet Res. 2003;34(5):521–64.PubMedGoogle Scholar
  28. 28.
    Kanneganti TD, Lamkanfi M, Nunez G. Intracellular NOD-like receptors in host defense and disease. Immunity. 2007;27(4):549–59.PubMedGoogle Scholar
  29. 29.
    Rainard P, Riollet C. Innate immunity of the bovine mammary gland. Vet Res. 2006;37(3):369–400.PubMedGoogle Scholar
  30. 30.
    Lee JY, Hwang DH. The modulation of inflammatory gene expression by lipids: mediation through toll-like receptors. Mol Cells. 2006;21(2):174–85.PubMedGoogle Scholar
  31. 31.
    Taraktsoglou M, Szalabska U, Magee DA, et al. Transcriptional profiling of immune genes in bovine monocyte-derived macrophages exposed to bacterial antigens. Vet Immunol Immunopathol. 2011;140(1–2):130–9.PubMedGoogle Scholar
  32. 32.
    Wright SD, Ramos RA, Tobias PS, et al. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990;249(4975):1431–3.PubMedGoogle Scholar
  33. 33.
    Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406(6797):782–7.PubMedGoogle Scholar
  34. 34.
    Henneke P, Morath S, Uematsu S, et al. Role of lipoteichoic acid in the phagocyte response to group B streptococcus. J Immunol. 2005;174(10):6449–55.PubMedGoogle Scholar
  35. 35.
    Schroder NW, Morath S, Alexander C, et al. Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem. 2003;278(18):15587–94.PubMedGoogle Scholar
  36. 36.
    Franchini M, Schweizer M, Matzener P, et al. Evidence for dissociation of TLR mRNA expression and TLR agonist-mediated functions in bovine macrophages. Vet Immunol Immunopathol. 2006;110(1–2):37–49.PubMedGoogle Scholar
  37. 37.
    Paape MJ, Bannerman DD, Zhao X, et al. The bovine neutrophil: structure and function in blood and milk. Vet Res. 2003;34(5):597–627.PubMedGoogle Scholar
  38. 38.
    Medina E. Neutrophil extracellular traps: a strategic tactic to defeat pathogens with potential consequences for the host. J Innate Immun. 2009;1(3):176–80.PubMedGoogle Scholar
  39. 39.
    Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5.PubMedGoogle Scholar
  40. 40.
    Yu C, Shi ZR, Chu CY, et al. Expression of bovine granulocyte chemotactic protein-2 (GCP-2) in neutrophils and a mammary epithelial cell line (MAC-T) in response to various bacterial cell wall components. Vet J. 2010;186(1):89–95.PubMedGoogle Scholar
  41. 41.
    Stevens MG, Peelman LJ, De Spiegeleer B, et al. Differential gene expression of the toll-like receptor-4 cascade and neutrophil function in early- and mid-lactating dairy cows. J Dairy Sci. 2011;94(3):1277–88.PubMedGoogle Scholar
  42. 42.
    Guo RF, Riedemann NC, Ward PA. Role of C5a-C5aR interaction in sepsis. Shock. 2004;21(1):1–7.PubMedGoogle Scholar
  43. 43.
    Stevens MG, Van Poucke M, Peelman LJ, et al. Anaphylatoxin C5a-induced toll-like receptor 4 signaling in bovine neutrophils. J Dairy Sci. 2011;94(1):152–64.PubMedGoogle Scholar
  44. 44.
    Worku M, Morris A. Binding of different forms of lipopolysaccharide and gene expression in bovine blood neutrophils. J Dairy Sci. 2009;92(7):3185–93.PubMedGoogle Scholar
  45. 45.
    Sohn EJ, Paape MJ, Connor EE, et al. Bacterial lipopolysaccharide stimulates bovine neutrophil production of TNF-alpha, IL-1beta, IL-12 and IFN-gamma. Vet Res. 2007;38(6):809–18.PubMedGoogle Scholar
  46. 46.
    Yang W, Zerbe H, Petzl W, et al. 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. 2008;45(5):1385–97.PubMedGoogle Scholar
  47. 47.
    Hattar K, Grandel U, Moeller A, et al. Lipoteichoic acid (LTA) from Staphylococcus aureus stimulates human neutrophil cytokine release by a CD14-dependent, Toll-like-receptor-independent mechanism: Autocrine role of tumor necrosis factor-[alpha] in mediating LTA-induced interleukin-8 generation. Crit Care Med. 2006;34(3):835–41.PubMedGoogle Scholar
  48. 48.
    Riollet C, Rainard P, Poutrel B. Cell subpopulations and cytokine expression in cow milk in response to chronic Staphylococcus aureus infection. J Dairy Sci. 2001;84(5):1077–84.PubMedGoogle Scholar
  49. 49.
    Arditi M, Zhou J, Dorio R, et al. Endotoxin-mediated endothelial cell injury and activation: role of soluble CD14. Infect Immun. 1993;61(8):3149–56.PubMedGoogle Scholar
  50. 50.
    Van Oostveldt K, Paape MJ, Dosogne H, et al. Effect of apoptosis on phagocytosis, respiratory burst and CD18 adhesion receptor expression of bovine neutrophils. Domest Anim Endocrinol. 2002;22(1):37–50.PubMedGoogle Scholar
  51. 51.
    Hoeben D, Burvenich C, Trevisi E, et al. Role of endotoxin and TNF-alpha in the pathogenesis of experimentally induced coliform mastitis in periparturient cows. J Dairy Res. 2000;67(4):503–14.PubMedGoogle Scholar
  52. 52.
    Wenz JR, Barrington GM, Garry FB, et al. Bacteremia associated with naturally occuring acute coliform mastitis in dairy cows. J Am Vet Med Assoc. 2001;219(7):976–81.PubMedGoogle Scholar
  53. 53.
    Fleck A. Clinical and nutritional aspects of changes in acute-phase proteins during inflammation. Proc Nutr Soc. 1989;48(3):347–54.PubMedGoogle Scholar
  54. 54.
    Vels L, Rontved CM, Bjerring M, et al. Cytokine and acute phase protein gene expression in repeated liver biopsies of dairy cows with a lipopolysaccharide-induced mastitis. J Dairy Sci. 2009;92(3):922–34.PubMedGoogle Scholar
  55. 55.
    Jiang L, Sorensen P, Rontved C, et al. Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide. BMC Genomics. 2008;9:443.PubMedGoogle Scholar
  56. 56.
    Bruzzone P, Siegel JH, Chiarla C, et al. Leucine dose response in the reduction of urea production from septic proteolysis and in the stimulation of acute-phase proteins. Surgery. 1991;109(6):768–78.PubMedGoogle Scholar
  57. 57.
    Bertoni G, Trevisi E, Han X, et al. Effects of inflammatory conditions on liver activity in puerperium period and consequences for performance in dairy cows. J Dairy Sci. 2008;91(9):3300–10.PubMedGoogle Scholar
  58. 58.
    Bionaz M, Trevisi E, Calamari L, et al. Plasma paraoxonase, health, inflammatory conditions, and liver function in transition dairy cows. J Dairy Sci. 2007;90(4):1740–50.PubMedGoogle Scholar
  59. 59.
    Drackley JK. ADSA Foundation Scholar Award. Biology of dairy cows during the transition period: the final frontier? J Dairy Sci. 1999;82(11):2259–73.PubMedGoogle Scholar
  60. 60.
    Reynolds CK, Harmon DL, Cecava MJ. Absorption and delivery of nutrients for milk protein synthesis by portal-drained viscera. J Dairy Sci. 1994;77(9):2787–808.PubMedGoogle Scholar
  61. 61.
    Drackley JK, Dann HM, Douglas GN, et al. Physiological and pathological adaptations in dairy cows that may increase susceptibility to periparturient diseases and disorders. Ital J Anim Sci. 2005;4(4):323–44.Google Scholar
  62. 62.
    Desruisseaux MS, Nagajyothi F, Trujillo ME, et al. Adipocyte, adipose tissue, and infectious disease. Infect Immun. 2007;75(3):1066–78.PubMedGoogle Scholar
  63. 63.
    Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.PubMedGoogle Scholar
  64. 64.
    Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8(7):731–7.PubMedGoogle Scholar
  65. 65.
    Mukesh M, Bionaz M, Graugnard DE, et al. Adipose tissue depots of Holstein cows are immune responsive: inflammatory gene expression in vitro. Domest Anim Endocrinol. 2010;38(3):168–78.PubMedGoogle Scholar
  66. 66.
    Khovidhunkit W, Kim MS, Memon RA, et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res. 2004;45(7):1169–96.PubMedGoogle Scholar
  67. 67.
    Janovick NA, Boisclair YR, Drackley JK. Prepartum dietary energy intake affects metabolism and health during the periparturient period in primiparous and multiparous Holstein cows. J Dairy Sci. 2011;94(3):1385–400.PubMedGoogle Scholar
  68. 68.
    Barkema HW, Schukken YH, Lam TJ, et al. Incidence of clinical mastitis in dairy herds grouped in three categories by bulk milk somatic cell counts. J Dairy Sci. 1998;81(2):411–9.PubMedGoogle Scholar
  69. 69.
    Sordillo LM, Contreras GA, Aitken SL. Metabolic factors affecting the inflammatory response of periparturient dairy cows. Anim Health Res Rev. 2009;10(1):53–63.PubMedGoogle Scholar
  70. 70.
    Ingvartsen KL, Moyes KM. Nutrition, immune function and health of herbivores. Advances in Animal Bioscience 2011(In Press).Google Scholar
  71. 71.
    Moyes KM, Drackley JK, Morin DE, et al. Predisposition of cows to mastitis in non-infected mammary glands: effects of dietary-induced negative energy balance during mid-lactation on immune-related genes. Funct Integr Genomics. 2011;11(1):151–6.PubMedGoogle Scholar
  72. 72.
    Moyes KM, Drackley JK, Morin DE, et al. Greater expression of TLR2, TLR4, and IL6 due to negative energy balance is associated with lower expression of HLA-DRA and HLA-A in bovine blood neutrophils after intramammary mastitis challenge with Streptococcus uberis. Funct Integr Genomics. 2010;10(1):53–61.PubMedGoogle Scholar
  73. 73.
    Loor JJ, Everts RE, Bionaz M, et al. Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows. Physiol Genomics. 2007;32(1):105–16.PubMedGoogle Scholar
  74. 74.
    McCarthy SD, Waters SM, Kenny DA, et al. Negative energy balance and hepatic gene expression patterns in high-yielding dairy cows during the early postpartum period: a global approach. Physiol Genomics. 2010;42A(3):188–99.PubMedGoogle Scholar
  75. 75.
    Wathes DC, Cheng Z, Chowdhury W, et al. Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows. Physiol Genomics. 2009;39(1):1–13.PubMedGoogle Scholar
  76. 76.
    Morris DG, Waters SM, McCarthy SD, et al. Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity. Physiol Genomics. 2009;39(1):28–37.PubMedGoogle Scholar
  77. 77.
    Kimbrell DA, Beutler B. The evolution and genetics of innate immunity. Nat Rev Genet. 2001;2(4):256–67.PubMedGoogle Scholar
  78. 78.
    Pensa S, Watson CJ, Poli V. Stat3 and the inflammation/acute phase response in involution and breast cancer. J Mammary Gland Biol Neoplasia. 2009;14(2):121–9.PubMedGoogle Scholar
  79. 79.
    Piantoni P, Wang P, Drackley JK, et al. Expression of metabolic, tissue remodeling, oxidative stress, and inflammatory pathways in mammary tissue during involution in lactating dairy cows. Bioinform Biol Insights. 2010;4:85–97.PubMedGoogle Scholar
  80. 80.
    Nickerson SC. Immunological aspects of mammary involution. J Dairy Sci. 1989;72(6):1665–78.PubMedGoogle Scholar
  81. 81.
    Reed JR, Schwertfeger KL. Immune cell location and function during post-natal mammary gland development. J Mammary Gland Biol Neoplasia. 2010;15(3):329–39.PubMedGoogle Scholar
  82. 82.
    Griesbeck-Zilch B, Osman M, Kuhn C, et al. Analysis of key molecules of the innate immune system in mammary epithelial cells isolated from marker-assisted and conventionally selected cattle. J Dairy Sci. 2009;92(9):4621–33.PubMedGoogle Scholar
  83. 83.
    Rupp R, Boichard D. Genetics of resistance to mastitis in dairy cattle. Vet Res. 2003;34(5):671–88.PubMedGoogle Scholar
  84. 84.
    Bionaz M, Rodriguez-Zas SL, Everts RE, et al. MammOmics (TM): transcript profiling of the mammary gland during the lactation cycle in Holstein cows. J Dairy Sci. 2007;90:207–8.Google Scholar
  85. 85.
    Piantoni P, Hurley WL, Rodriguez-Zas SL, et al. Defining gene networks during involution of the mammary gland in dairy cows. J Dairy Sci. 2008;91(E-Suppl 1):819.Google Scholar
  86. 86.
    Rudolph MC, McManaman JL, Phang T, et al. Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine. Physiol Genomics. 2007;28(3):323–36.PubMedGoogle Scholar
  87. 87.
    Bionaz M, Loor JJ. Comparative MammOmics™ of milk fat synthesis in Mus musculus vs. Bos taurus. J Dairy Sci. 2008;91 Suppl 1:566–7.Google Scholar
  88. 88.
    Notebaert S, Meyer E. Mouse models to study the pathogenesis and control of bovine mastitis. A review Vet Q. 2006;28(1):2–13.Google Scholar
  89. 89.
    Brouillette E, Malouin F. The pathogenesis and control of Staphylococcus aureus-induced mastitis: study models in the mouse. Microbes Infect. 2005;7(3):560–8.PubMedGoogle Scholar
  90. 90.
    Rudolph MC, McManaman JL, Hunter L, et al. Functional development of the mammary gland: use of expression profiling and trajectory clustering to reveal changes in gene expression during pregnancy, lactation, and involution. J Mammary Gland Biol Neoplasia. 2003;8(3):287–307.PubMedGoogle Scholar
  91. 91.
    Zheng J, Watson AD, Kerr DE. Genome-wide expression analysis of lipopolysaccharide-induced mastitis in a mouse model. Infect Immun. 2006;74(3):1907–15.PubMedGoogle Scholar
  92. 92.
    Goudswaard J, Bakker-de Koff EC, van Ravenswaaij-Kraan HP. Lysozyme and its presence in bovine milk and serum. Tijdschr Diergeneeskd. 1978;103(8):445–50.PubMedGoogle Scholar
  93. 93.
    Ziegler-Heitbrock HW, Ulevitch RJ. CD14: cell surface receptor and differentiation marker. Immunol Today. 1993;14(3):121–5.PubMedGoogle Scholar
  94. 94.
    Atabai K, Sheppard D, Werb Z. Roles of the innate immune system in mammary gland remodeling during involution. J Mammary Gland Biol Neoplasia. 2007;12(1):37–45.PubMedGoogle Scholar
  95. 95.
    Oviedo-Boyso J, Valdez-Alarcon JJ, Cajero-Juarez M, et al. Innate immune response of bovine mammary gland to pathogenic bacteria responsible for mastitis. J Infect. 2007;54(4):399–409.PubMedGoogle Scholar
  96. 96.
    Paulsson KM. Evolutionary and functional perspectives of the major histocompatibility complex class I antigen-processing machinery. Cell Mol Life Sci. 2004;61(19–20):2446–60.PubMedGoogle Scholar
  97. 97.
    Fitzpatrick JL, Cripps PJ, Hill AW, et al. MHC class II expression in the bovine mammary gland. Vet Immunol Immunopathol. 1992;32(1–2):13–23.PubMedGoogle Scholar
  98. 98.
    Mejdell CM, Lie O, Solbu H, et al. Association of major histocompatibility complex antigens (BoLA-A) with AI bull progeny test results for mastitis, ketosis and fertility in Norwegian cattle. Anim Genet. 1994;25(2):99–104.PubMedGoogle Scholar
  99. 99.
    Sharif S, Mallard BA, Wilkie BN, et al. Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) alleles with occurrence of disease and milk somatic cell score in Canadian dairy cattle. Anim Genet. 1998;29(3):185–93.PubMedGoogle Scholar
  100. 100.
    Sharif S, Mallard BA, Wilkie BN. Characterization of naturally processed and presented peptides associated with bovine major histocompatibility complex (BoLA) class II DR molecules. Anim Genet. 2003;34(2):116–23.PubMedGoogle Scholar
  101. 101.
    Takeshima S, Matsumoto Y, Chen J, et al. Evidence for cattle major histocompatibility complex (BoLA) class II DQA1 gene heterozygote advantage against clinical mastitis caused by Streptococci and Escherichia species. Tissue Antigens. 2008;72(6):525–31.PubMedGoogle Scholar
  102. 102.
    Park YH, Joo YS, Park JY, et al. Characterization of lymphocyte subpopulations and major histocompatibility complex haplotypes of mastitis-resistant and susceptible cows. J Vet Sci. 2004;5(1):29–39.PubMedGoogle Scholar
  103. 103.
    Fitzpatrick JL, Mayer SJ, Vilela C, et al. Cytokine-induced major histocompatibility complex class II antigens on cultured bovine mammary gland epithelial cells. J Dairy Sci. 1994;77(10):2940–8.PubMedGoogle Scholar
  104. 104.
    Hackmann TJ, Spain JN. Invited review: ruminant ecology and evolution: perspectives useful to ruminant livestock research and production. J Dairy Sci. 2010;93(4):1320–34.PubMedGoogle Scholar
  105. 105.
    Mepham TB. Physiology of lactation. Milton Keynes; Philadelphia: Open University Press; 1987.Google Scholar
  106. 106.
    McVey Jr WR, Williams GL. Mechanical masking of neurosensory pathways at the calf-teat interface: endocrine, reproductive and lactational features of the suckled anestrous cow. Theriogenology. 1991;35(5):931–41.PubMedGoogle Scholar
  107. 107.
    Zwald NR, Weigel KA, Chang YM, et al. Genetic evaluation of dairy sires for milking duration using electronically recorded milking times of their daughters. J Dairy Sci. 2005;88(3):1192–8.PubMedGoogle Scholar
  108. 108.
    Rauw WM, Kanis E, Noordhuizen-Stassen EN, et al. Undesirable side effects of selection for high production efficiency in farm animals: a review. Livest Prod Sci. 1998;56(1):15–33.Google Scholar
  109. 109.
    Nielsen CB, Cantor M, Dubchak I, et al. Visualizing genomes: techniques and challenges. Nat Methods. 2010;7(3 Suppl):S5–S15.PubMedGoogle Scholar
  110. 110.
    O’Donoghue SI, Gavin AC, Gehlenborg N, et al. Visualizing biological data-now and in the future. Nat Methods. 2010;7(3 Suppl):S2–4.PubMedGoogle Scholar
  111. 111.
    Hettinga K, van Valenberg H, de Vries S, et al. The host defense proteome of human and bovine milk. PLoS One. 2011;6(4):e19433.PubMedGoogle Scholar
  112. 112.
    Lemay DG, Neville MC, Rudolph MC, et al. Gene regulatory networks in lactation: identification of global principles using bioinformatics. BMC Syst Biol. 2007;1:56.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Juan J. Loor
    • 1
  • Kasey M. Moyes
    • 2
  • Massimo Bionaz
    • 3
  1. 1.Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional SciencesUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Department of Animal Science, Faculty of Agricultural SciencesAarhus UniversityTjeleDenmark
  3. 3.Institute of Genomic BiologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA

Personalised recommendations