Mycobacterium avium subsp.
paratuberculosis (MAP) is the causative agent of bovine
paratuberculosis, a chronic
granulomatous enteritis leading to economic losses and posing a risk to human health due to its zoonotic potential. The pathogen cannot reliably be detected by standard methods, and immunological procedures during the
infection are not well understood. Therefore, the aim of our study was to explore host-pathogen interactions in MAP-infected dairy cows and to improve diagnostic tests. Serum proteomics analysis using quantitative label-free LC-MS/MS revealed 60 differentially abundant
proteins in MAP-infected dairy cows compared to healthy controls from the same infected herd and 90 differentially abundant
proteins in comparison to another control group from an uninfected herd. Pathway enrichment analysis provided new insights into the immune response to MAP and susceptibility to the
infection. Furthermore, we found a higher abundance of
Cathepsin S (CTSS) in the serum of MAP-infected dairy cows, which is involved in multiple enriched pathways associated with the immune system. Confirmed with Western blotting, we identified CTSS as a potential
biomarker for bovine
paratuberculosis. This study enabled a better understanding of procedures in the host-pathogen response to MAP and improved detection of
paratuberculosis-diseased cattle.