Mycobacterium avium subsp. paratuberculosis Infected Cows Reveal Divergent Immune Response in Bovine Peripheral Blood Derived Lymphocyte Proteome

Abstract

Bovine paratuberculosis is a serious chronic disease of the gastrointestinal tract that causes economic losses and dramatically affects animal health in livestock. The underlying infectious agent, Mycobacterium avium subspecies paratuberculosis (MAP), cannot reliably be detected by standard diagnostic tests due to the long asymptomatic disease stage. The aim of this study was to detect proteomic changes in peripheral blood mononuclear cells (PBMC) from cows of the same herd with different MAP infection status after co-incubation with viable MAP in vitro using label-free LC-MS/MS. In our proteomic discovery experiment, we detected 2631 differentially regulated proteins between cows with negative MAP infection status (so-called MAP-resistant cows) and cows with positive MAP infection status (so-called persistently MAP-infected cows). In MAP-resistant cows, we detected enriched immune-related signaling pathways for TLR2 and MHC class II component proteins, among others, indicating a successful defensive immune response of the cows to MAP. In contrast, persistently MAP-infected cows were not directly enriched in immune-related signaling pathways associated with ITGA2B and KCNMA1, among others. The introduction of these distinct immune responses contributes to a better understanding of the bovine immune response and mechanisms of susceptibility to MAP.

Cathepsin S Is More Abundant in Serum of Mycobacterium avium subsp. paratuberculosis-Infected Dairy Cows

“…In vitro, MAP-infected bovine macrophages showed downregulation of MHC class II expression, which appears to be a strategy of MAP to secure their survival by inhibiting efficient mycobacterial antigen presentation to T cells [75]. In our previous in vitro study with PBMCs co-incubated with MAP, we observed a higher abundance of MHC class II complex proteins in MAP-resistant cows compared to persistently MAP-infected cattle [36], which describes an association of the expression of MHC class II with resistance to MAP. In our serum proteome analysis, we detected a higher abundance of BOLA-DRA in the serum of MAP-infected cows compared to both healthy control groups (Figure 1a,b).…”

“…In the PBMCs of the control group, we showed a higher abundance of IL-12-mediated signaling pathways, while we observed a higher abundance of CCR4-NOT transcription complex, subunit 1 in immune deviant cows, which may promote infectious diseases by repressing MHC class II expression [34,35]. In another co-incubation study of MAP and the PBMCs of cows with different MAP infection statuses, we detected a defensive immune response of MAP-infected cows to MAP, realized by an increased abundance of the involved proteins toll-like receptor 2 and major histocompatibility complex (MHC) class II [36]. These findings underscore the complexity of the immune response to MAP and highlight the need for further investigation into factors that contribute to the persistence of MAP in cattle.…”

Development of Nested Polymerase Chain Reaction with Novel Specific Primers for Detection of Tritrichomonas muris Infection in Laboratory Mice

“…In view of these findings, it may be beneficial to prioritize the need to strengthen the management of experimental animal housing and detect animal health whenever possible [61]. Therefore, to prevent T. muris infections, animal breeding laws and regulations should be improved [62][63][64]. The following aspects should be improved: (i) Increasing awareness of the importance of clean and SPF animal production and the health and epidemic prevention of animal houses [62,65,66].…”