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The role of natural killer cells in modulating the immune response in bovine E. coli mastitis

Applicant Dr. Anja Sipka
Subject Area Veterinary Medical Science
Immunology
Term from 2013 to 2015
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 246128117
 
Final Report Year 2016

Final Report Abstract

Natural killer (NK) cells are early responders in bacterial infections but until now their role in bovine mastitis has not been characterized. The objective of this study was to investigate the presence of bovine NK cells in the bovine mammary gland and their immune regulatory potential and antimicrobial properties in vitro. For the first time, we demonstrated the presence of NK cells (NKp46+/CD3‐) in bovine mammary gland tissue after an intramammary challenge with Escherichia (E.) coli. A small number of NK cells was detected in milk from quarters before and during an E. coli challenge. In vitro cultures of primary bovine mammary gland epithelial cells stimulated with UV irradiated E. coli induced significant migration of NK cells within 2h. Furthermore, NK cells significantly reduced counts of live E. coli in vitro within 2h of culture. The results show that bovine NK cells have the capacity to migrate to the site of infection and produce antibacterial mediators. These findings introduce NK cells as a leukocyte population in the mammary gland with potential key functions in immune regulation in bovine mastitis. The reciprocal cross‐talk between NK cells and dendritic cells (DC) in the presence of pathogens leads to potent activation of both cell types. We investigated whether activation of bovine NK cells can occur after co‐culture with immature monocyte derived DC (iDC) in the absence of pathogens. Activation of NK cells was assessed by expression of CD25, changes in cell morphology and production of the pro‐inflammatory cytokine IFN‐γ. Co‐culture with iDC significantly increased the percentage of CD25+ NK cells. Expression levels were comparable to co‐culture of NK cells with E.coli stimulated, mature DC (mDC). However, a significant increase in cell complexity and IFN‐γ ‐production in NK cells could only be observed after co‐culture with stimulated, mDC. The presence of NK cells increased MHCII expression in both, iDC and mDC, inducing an expression pattern in iDC similar to mDC. The results indicate that bovine NK cells can become activated by DC that did not have previous pathogen contact and in return modulate antigen presenting capacities in iDC. A potential interplay between bovine NK cells and iDC under steady state conditions in peripheral tissue could influence the immune response after pathogen contact and the capacity of the host to eliminate the infection.

Publications

  • New insights in the role of Natural Killer cells in bovine E. coli mastitis. 5th European Veterinary Immunology Workshop, Vienna, September 2nd – 4th 2015
    Anja Sipka, Brianna Pomeroy, Suzanne Klaessig, Ynte Schukken
  • Bovine natural killer cells are present in Escherichia coli infected mammary gland tissue and show antimicrobial activity in vitro. Comparative Immunology, Microbiology & Infectious Diseases, Volume 48, October 2016, Pages 54-60
    Anja Sipka, Brianna Pomeroy, Suzanne Klaessig, Ynte Schukken
    (See online at https://doi.org/10.1016/j.cimid.2016.08.001)
 
 

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