A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence.

Karina Lutterberg,Stefan Nüske,Bernhard F. Hobmaier,Kristina J. H. Kleinwort,Armin M. Scholz,Cornelia A. Deeg,Stefanie M. Hauck

doi:10.3389/fimmu.2018.02884

Abstract

A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5–10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.

Highlights

Vaccines are the most effective and affordable disease-prevention tools [1] and maternal antibodies protect the offspring from infections in man [2] and animals [3]
To exclude differences in lymphocyte subset percentages between control and bovine neonatal pancytopenia (BNP) dams as a possible cause for the differential responses toward polyclonal immune stimulation, we analyzed the distribution of CD4+, CD8+, and B cells in control and BNP peripheral blood derived lymphocytes (PBL)
Our findings proved a STAT3 pathway dependent immune response of BNP lymphocytes after polyclonal stimulation, but so far it is unknown which T helper (Th) subsets exactly are regulated by STAT3 in cows

Summary

Introduction

Vaccines are the most effective and affordable disease-prevention tools [1] and maternal antibodies protect the offspring from infections in man [2] and animals [3]. A novel production technology using an allogeneic cell line [6] and the addition of a highly potent adjuvant to PregSure BVD, a new vaccine against bovine viral diarrhea (BVD), induced fatal immune reactions with production of alloreactive antibodies in 5–10% of vaccinated cows [7,8,9] These alloantibodies were transmitted to calves, regardless of kin, via the colostrum of these dams [8, 10] and caused bovine neonatal pancytopenia (BNP) [7, 11,12,13], even years after the vaccine has been taken off the market [14].

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Results

Conclusion