Skip to main content

Cells and Cytokines in Inflammatory Secretions of Bovine Mammary Gland

  • Chapter
Book cover Biology of the Mammary Gland

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 480))

Abstract

In response to invading bacteria, the mammary gland is protected by a variety of defence mechanisms, which can be separated into two distinct categories: innate immunity and specific immunity. Milk somatic cells consist of several cell types, including neutrophils, macrophages, lymphocytes and a smaller percentage of epithelial cells. In the healthy lactating mammary gland, macrophages are the predominant cell type whereas neutrophils are the major cell population during early inflammation. Following a bacteria invasion, neutrophil recruitment is elicited by inflammatory mediators that are produced in the infected gland by cells, possibly macrophages, activated by bacteria phagocytosis or responding to bacterial toxins or metabolites. Several cytokines,including interleukin-(IL-)1 β, IL-6, IL-8, tumour necrosis factor-(TNF-)α and interferon-(IFN-) γ are known to be important to elicit the acute phase response and allow the accumulation of leukocytes at the site of infection. In addition to their role in early non-specific defences, macrophages also play a key role in the specific immune system, as antigen processing and presenting cells for the T cells. Few lymphocytes are found in milk of healthy glands where the predominant phenotype is CD8+ T cells. During the inflammatory reaction, T cells are recruited in milk and CD4+ cells become the predominant phenotype. The understanding of the specific and non-specific immune mechanisms involved in the mammary gland defence against invading bacteria may lead to the development of new vaccines and to the use of cytokines to design immunomodulatory strategies for the control of bovine mastitis.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agace WW, Hedges SR, Ceska M, Svanborg C. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. J Clin Invest 2, 780–785, 1993.

    Google Scholar 

  2. Allison JP, Havran WL. The immunobiology of T cells with invariant gamma delta antigen receptors. Annu Rev Immunol, 679–705, 1991.

    Google Scholar 

  3. Bertotto A, Gerli R, Fabietti G, Crupi S, Arcangeli C, Scalise F, Vaccaro R. Human breast milk T lymphocytes display the phenotype and functional characteristics of memory T cells. Eur J Immunol 8, 1877–1880, 1990.

    Google Scholar 

  4. Beuscher HU, Rodel F, Forsberg A, Rollinghoff M. Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression. Infect Immun 4, 1270–1277, 1995.

    Google Scholar 

  5. Boudjellab N, Chang-Tang HS, Li X, Zhao X. Interleukin-8 respons by bovine mammary epithelial cells to lipopolysaccharide stimulation. Am J Vet Res, 1563–1567, 1998.

    Google Scholar 

  6. Brown WC, Rice-Ficht AC, Estes DM. Bovine type 1 and type 2 responses. Vet Immunol Immunopathol 1–2, 45–55, 1998.

    Google Scholar 

  7. Brown WC, Woods VM, Chitko-McKown CG, Hash SM, Rice-Ficht AC. Interleukin-10 is expressed by bovine type 1 helper, type 2 helper, and unrestricted parasite-specific T-cell clones and inhibits proliferation of all three subsets in an accessory-cell-dependent manner. Infect Immun 11, 4697–4708, 1994.

    Google Scholar 

  8. Cassatella MA. The production of cytokines by polymorphonuclear neutrophils. Immunol Today 1, 21–26, 1995.

    Google Scholar 

  9. Cassatella MA. Neutrophil-derived proteins: selling cytokines by the pound. Adv Immunol, 369–509, 1999.

    Google Scholar 

  10. Chiodini RJ, Davis WC. The cellular immunology of bovine paratuberculosis: immunity may be regulated by CD4+ helper and CD8+ immunoregulatory T lymphocytes which down-regulate gamma/delta+ T-cell cytotoxicity. Microb Pathog 5, 355–367, 1993.

    Google Scholar 

  11. Colditz IG, Zwahlen RD, Baggiolini M. Neutrophil accumulation and plasma leakage induced in vivo by neutrophil-activating peptide-1. J Leukoc Biol 2, 129–137, 1990.

    Google Scholar 

  12. Concha C, Holmberg O, Astrom G. Cells found in non-infected and staphylococcus-infected bovine mammary quarters and their ability to phagocytose fluorescent microspheres. Zentralbl Veterinarmed [B] 5, 371–378, 1986.

    Google Scholar 

  13. Craven N. Generation of neutrophil chemoattractants by phagocytosing bovine mammary macrophages. Res Vet Sci 3, 310–317, 1983.

    Google Scholar 

  14. Daley MJ, Coyle PA, Williams TJ, Furda G, Dougherty R, Hayes PW. Staphylococcus aureus mastitis: pathogenesis and treatment with bovine interleukin-1 beta and interleukin-2. J Dairy Sci 12, 4413–4424, 1991.

    Google Scholar 

  15. Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S. Human IL-10 is produced by both type 1 helper (Th 1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 2, 353–360, 1993.

    Google Scholar 

  16. Denis M, Campbell D, Gregg EO. Interleukin-2 and granulocyte-macrophage colony-stimulating factor stimulate growth of a virulent strain of Escherichia coli. Infect Immun 5, 1853–1856, 1991.

    Google Scholar 

  17. Dinarello CA. Interleukin-1. Adv Pharmacol, 21–51, 1994.

    Google Scholar 

  18. Eberhart RJ, Natzke RP, Newbould FHS. Coliform mastitis —a review. J Dairy Sci, 1–22, 1979.

    Google Scholar 

  19. Eckmann L, Kagnoff MF, Fierer J. Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry. Infect Immun 11, 4569–4574, 1993.

    Google Scholar 

  20. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 6, 2081–2095, 1989.

    Google Scholar 

  21. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol 11, 3815–3822, 1991a.

    Google Scholar 

  22. Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 10, 3444–3451, 1991.

    Google Scholar 

  23. Fitzpatrick JL, Cripps PJ, Hill AW, Bland PW, Stokes CR. MHC class II expression in the bovine mammary gland. Vet Immunol Immunopathol 1–2, 13–23, 1992.

    Google Scholar 

  24. Gajewski TF, Fitch FW. Anti-proliferative effect of IFN-gamma in immune regulation. I.IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol 12, 4245–4252, 1988.

    Google Scholar 

  25. Harmon RJ, Heald CW. Migration of polymorphonuclear leukocytes into the bovine mammary gland during experimentally induced Staphylococcus aureus mastitis. Am J Vet Res 6, 992–998, 1982.

    Google Scholar 

  26. Hein WR, Mackay CR. Prominence of gamma delta T cells in the ruminant immune system. Immunol Today 1, 30–34, 1991.

    Google Scholar 

  27. Henderson, B. and Bodmer, M. In Therapeutic modulation of cytokines. Boca Raton: CRC Press 1996.

    Google Scholar 

  28. Henderson B, Poole S. Modulation of cytokine function: therapeutic applications. Adv Pharmacol, 53–115, 1994.

    Google Scholar 

  29. Henderson B, Poole S, Wilson M. Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis. Microbiol Rev 2, 316–341, 1996a.

    Google Scholar 

  30. Henderson B, Poole S, Wilson M. Microbial/host interactions in health and disease: who controls the cytokine network? Immunopharmacology 1, 1–21, 1996b.

    Google Scholar 

  31. Huber AR, Kunkel SL, Todd RF, Weiss SJ. Regulation of transendothelial neutrophil migration by endogenous interleukin-8 [published errata appear in Science 1991 Nov 1;254(5032):631 and 1991 Dec 6;254(5037):1435]. Science 5028, 99–102, 1991.

    Google Scholar 

  32. Inoue T, Asano Y, Matsuoka S, Furutani-Seiki M, Aizawa S, Nishimura H, Shirai T, Tada T. Distinction of mouse CD8+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms. J Immunol 6, 2121–2128, 1993.

    Google Scholar 

  33. Jackson JA, Shuster DE, Silvia WJ, Harmon RJ. Physiological responses to intramammary or intravenous treatment with endotoxin in lactating dairy cows. J Dairy Sci 3, 627–632, 1990.

    Google Scholar 

  34. Kelso A. Th1 and Th2 subsets: paradigms lost? Immunol Today 8, 374–379, 1995.

    Google Scholar 

  35. Kishimoto TK, Jutila MA, Berg EL, Butcher EC. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science 4923, 1238–1241, 1989.

    Google Scholar 

  36. Larsen CG, Anderson AO, Oppenheim JJ, Matsushima K. Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumour necrosis factor. Immunology 1, 31–36, 1989.

    CAS  Google Scholar 

  37. Lee CS, Wooding FB, Kemp P. Identification, properties, and differential counts of cell populations using electron microscopy of dry cows secretions, colostrum and milk from normal cows. J Dairy Res 1, 39–50, 1980.

    CAS  Google Scholar 

  38. Lloyd AR, Oppenheim JJ. Poly’s lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunol Today 5, 169–172, 1992.

    Google Scholar 

  39. Lohuis JA, Verheijden JH, Burvenich C, van Miert AS. Pathophysiological effects of endotoxins in ruminants. 1. Changes in body temperature and reticulo-rumen motility, and the effect of repeated administration. Vet Q 2, 109–116, 1988.

    Google Scholar 

  40. Mackay CR, Hein WR. Marked variations in gamma delta T cell numbers and distribution throughout the life of sheep. Curr Top Microbiol Immunol, 107–111, 1991.

    Google Scholar 

  41. Mackay CR, Hein WR, Brown MH, Matzinger P. Unusual expression of CD2 in sheep: implications for T cell interactions. Eur J Immunol 11, 1681–1688, 1988.

    Google Scholar 

  42. Marchant A, JL Vincent, M Goldman. In Novel therapeutic strategies in the treatment of sepsis. New York: Marcel Dekker 1996.

    Google Scholar 

  43. Matsukawa A, Yoshinaga M. Neutrophils as a source of cytokines in inflammation. Histol Histopathol 2, 511–516, 1999.

    Google Scholar 

  44. Mehrotra PT, Wu D, Crim JA, Mostowski HS, Siegel JP. Effects of IL-12 on the generation of cytotoxic activity in human CD8+ T lymphocytes. J Immunol 5, 2444–2452, 1993.

    Google Scholar 

  45. Miller RH, Paape MJ, Fulton LA. Variation in milk somatic cells of heifers at first calving. J Dairy Sci 11, 3782–3790, 1991.

    Google Scholar 

  46. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol, 145–173, 1989.

    Google Scholar 

  47. Outteridge PM, Lee CS. Cellular immunity in the mammary gland with particular reference to T, B lymphocytes and macrophages. Adv Exp Med Biol, 513–534, 1981.

    Google Scholar 

  48. Park YH, Fox LK, Hamilton MJ, Davis WC. Bovine mononuclear leukocyte subpopulations in peripheral blood and mammary gland secretions during lactation. J Dairy Sci 4, 998–1006, 1992.

    Google Scholar 

  49. Park YH, Fox LK, Hamilton MJ, Davis WC. Suppression of proliferative response of BoCD4+ T lymphocytes by activated BoCD8+ T lymphocytes in the mammary gland of cows with Staphylococcus aureus mastitis. Vet Immunol Immunopathol 2, 137–151, 1993.

    Google Scholar 

  50. Persson K, Larsson I, Hallen SC. Effects of certain inflammatory mediators on bovine neutrophil migration in vivo and in vitro. Vet Immunol Immunopathol 2, 99–112, 1993.

    Google Scholar 

  51. Politis I, Zhao X, McBride BW, Burton JH. Function of bovine mammary macrophages as antigen-presenting cells. Vet Immunol Immunopathol 4, 399–410, 1992.

    Google Scholar 

  52. Porat R, Clark BD, Wolff SM, Dinarello CA. Enhancement of growth of virulent strains of Escherichia coli by interleukin-I [see comments]. Science 5030, 430–432, 1991.

    Google Scholar 

  53. Reddy PG, Reddy DN, Pruiett SE, Daley MJ, Shirley JE, Chengappa MM, Blecha F. Interleukin 2 treatment of Staphylococcus aureus mastitis. Cytokine 3, 227–231, 1992.

    Google Scholar 

  54. Riollet C, Rainard P, Poutrel B. Cell subpopulations and cytokine expression in bovine milk in response to chronic Staphylococcus aureus infection. submitted for publication, 1999.

    Google Scholar 

  55. Sample AK, Czuprynski CJ. Priming and stimulation of bovine neutrophils by recombinant human interleukin-1 alpha and tumor necrosis factor alpha. J Leukoc Biol 2, 107–115, 1991.

    Google Scholar 

  56. Seder RA, Paul WE, Davis MM, Fazekas dS. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. J Exp Med 4, 1091–1098, 1992.

    Google Scholar 

  57. Selsted ME, Tang YQ, Morris WL, McGuire PA, Novotny MJ, Smith W, Henschen AH, Cullor JS. Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. J Biol Chem 9, 6641–6648, 1993.

    Google Scholar 

  58. Shafer-Weaver KA, Corl CM, Sordillo LM. Shifts in bovine CD4+ subpopulations increase T-helper-2 compared with T-helper-1 effector cells during the postpartum period. J Dairy Sci, 1696–1706, 1999.

    Google Scholar 

  59. Shafer-Weaver KA, Sordillo LM. Bovine CD8+ suppressor lymphocytes alter immune responsiveness during the postpartum period. Vet Immunol Immunopathol 1–2, 53–64, 1997.

    Google Scholar 

  60. Shuster DE, Kehrli MEJ, Rainard P, Paape M. Complement fragment C5a and inflammatory cytokines in neutrophil recruitment during intramammary infection with Escherichia coli. Infect Immun 8, 3286–3292,1997.

    Google Scholar 

  61. Shuster DE, Kehrli MEJ, Stevens MG. Cytokine production during endotoxin-induced mastitis in lactating dairy cows. Am J Vet Res 1, 80–85, 1993.

    Google Scholar 

  62. Shuster DE, Lee EK, Kehrli MEJ. Bacterial growth, inflammatory cytokine production, and neutrophil recruitment during coliform mastitis in cows within ten days after calving, compared with cows at midlactation. Am J Vet Res 11, 1569–1575, 1996.

    Google Scholar 

  63. Sordillo LM, Babiuk LA. Controlling acute Escherichia coli mastitis during the periparturient period with recombinant bovine interferon gamma. Vet Microbiol 2, 189–198, 1991a.

    Google Scholar 

  64. Sordillo LM, Babiuk LA. Modulation of bovine mammary neutrophil function during the periparturient period following in vitro exposure to recombinant bovine interferon gamma. Vet Immunol Immunopathol 4, 393–402, 1991b.

    Google Scholar 

  65. Sordillo LM, Shafer-Weaver K, DeRosa D. Immunobiology of the mammary gland. J Dairy Sci 8, 1851–1865, 1997.

    Google Scholar 

  66. Steinbeck MJ, Roth JA. Neutrophil activation by recombinant cytokines. Rev Infect Dis 4, 549–568, 1989.

    Google Scholar 

  67. Taylor BC, Dellinger JD, Cullor JS, Stott JL. Bovine milk lymphocytes display the phenotype of memory T cells and are predominantly CD8+. Cell Immunol 1, 245–253, 1994.

    Google Scholar 

  68. Taylor BC, Keefe RG, Dellinger JD, Nakamura Y, Cullor JS, Stott JL. T cell populations and cytokine expression in milk derived from normal and bacteria-infected bovine mammary glands. Cell Immunol 1, 68–76, 1997.

    Google Scholar 

  69. Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol, 251–276, 1995.

    Google Scholar 

  70. Wirt DP, Adkins LT, Palkowetz KH, Schmalstieg FC, Goldman AS. Activated and memory T lymphocytes in human milk. Cytometry 3, 282–290, 1992.

    Google Scholar 

  71. Yang TJ, Ayoub IA, Rewinski MJ. Lactation stage-dependent changes of lymphocyte subpopulations in mammary secretions: inversion of CD4+/CD8+ T cell ratios at parturition. Am J Reprod Immunol 5, 378–383, 1997.

    Google Scholar 

  72. Yssel H, De Waal M, Roncarolo MG, Abrams JS, Lahesmaa R, Spits H, de Vries JE. IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol 7, 2378–2384, 1992.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Kluwer Academic Publishers

About this chapter

Cite this chapter

Riollet, C., Rainard, P., Poutrel, B. (2002). Cells and Cytokines in Inflammatory Secretions of Bovine Mammary Gland. In: Mol, J.A., Clegg, R.A. (eds) Biology of the Mammary Gland. Advances in Experimental Medicine and Biology, vol 480. Springer, Boston, MA. https://doi.org/10.1007/0-306-46832-8_30

Download citation

  • DOI: https://doi.org/10.1007/0-306-46832-8_30

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46414-0

  • Online ISBN: 978-0-306-46832-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics