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

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.

Interplay of primary bovine lymphocytes and Mycobacterium avium subsp. paratuberculosis shows distinctly different proteome changes and immune pathways in host-pathogen interaction

“…In the post-genomic era, proteomics represents a key discipline to perform in depth studies and identify the complex network of proteins involved in such host-bacteria communication. In this study, we analysed the exoproteomes/secretomes of MAP and host cow PBL with known, functionally different immune capacities (Lutterberg et al, 2018) using differential proteome analyses after in vitro infection. Interestingly, there were significant differences in protein abundances secreted from control and ID PBL.…”

“…55.2-1-54-2532.3-22-12. For determination of control or ID status, PBL were tested in in vitro proliferation assays as described (Lutterberg et al, 2018). Respective animals were tested at least 11 times, before being assigned to control or ID status.…”

“…Recently, we detected a functionally different immune capacity in 22% of cows from different herds in Germany using differential proteome analyses (Lutterberg et al, 2018). These immune deviant (ID) cows differ in their constitutive immune proteome and they regulate different master immune regulators upon polyclonal immune cell stimulation.…”

“…These immune deviant (ID) cows differ in their constitutive immune proteome and they regulate different master immune regulators upon polyclonal immune cell stimulation. The phenotype is functionally correlated with an increased prevalence of mastitis, indicating an impact on the ability to fight infections (Lutterberg et al, 2018).…”

Peer Review #2 of "Peripheral blood bovine lymphocytes and MAP show distinctly different proteome changes and immune pathways in host-pathogen interaction (v0.2)"

“…Functional differences in these responses could lead to aberrant reactions in susceptible hosts (Davis 2015). Recently, we detected a functionally different immune capacity in 22% of cows from different herds in Germany using differential proteome analyses (Lutterberg et al 2018). These cows differ in their constitutive immune proteome and they regulate different master immune regulators upon polyclonal immune cell stimulation.…”