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Kleinwort, K. J. H.

Publications and source records attributed to Kleinwort, K. J. H..

3 recordsLinked to original sources

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

Mycobacterium avium subsp. paratuberculosis (MAP) is a pathogen causing paratuberculosis in cattle and small ruminants. During the long asymptomatic subclinical stage, high numbers of MAP are excreted and can be transmitted to food, where they survive many of the standard techniques of food decontamination. If these MAP are harmful to the consumers is currently under debate. In general, there is a lack of information regarding interaction of the hosts immune system with MAP.\n\nIn this study, we tested the interaction of peripheral blood lymphocytes (PBL) from cattle with MAP in their exoproteomes/secretomes. Because in other mycobacterial infections, the immune phenotype correlates with susceptibility, we additionally tested the interaction of MAP with recently detected immune deviant cows.\n\nIn PBL, different biological pathways were enhanced in response to MAP dependent on the immune phenotype of the host. PBL of control cows activated members of cell activation and chemotaxis of leukocytes pathway as well as IL-12 mediated signaling. In contrast, in ID cows CNOT1 was detected as highly abundant protein, pointing to a different immune response, which could be favorable for MAP. Additionally, MAP reacted different to the hosts. Their exoproteomes differed in either GroEL1 or DnaK abundance, depending on the interacting immune response.\n\nThese findings point to an interdependent, tightly regulated response of MAP and the immune system.

immunology↗

A functional different immune capacity in cattle is associated with higher mastitis incidence

Bovine neonatal pancytopenia (BNP) was a deadly disease transferred by antibodies from 5-10% of cows given a novel BVD vaccine. Disease was lethal in 90% of calves receiving colostrum with BNP antibodies. The cause of BNP is not fully understood to date. We revealed a profound difference in immune capacities between BNP dams and non-responders. Significant differences were detectable in response to in vitro stimulation of peripheral blood derived lymphocytes to several mitogens and IL-2. BNP cows regulated their immune proteomes completely different from controls with other immune response master regulators. Since we detected this response pattern also in 22% of cows that were never vaccinated at all, this immune deviant (ID) phenotype is still present in cattle and probably inherited. Immune response pattern of these cows was stable over an observation period of 38 months. Importantly, ID have a significant increased prevalence of mastitis underscoring the clinical importance.

immunology↗

Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights into signaling pathways associated with autoimmunity

The GTP-binding protein septin 7 is involved in various cellular processes, including cytoskeleton organization, migration and the regulation of cell shape. Septin 7 function in lymphocytes, however, is poorly characterized. Since the intracellular signaling role of septin 7 is dependent on its interaction network, interaction proteomics was applied to attain novel knowledge about septin 7 function in hematopoietic cells. Our previous finding of decreased septin 7 expression in blood-derived lymphocytes in ERU, a spontaneous animal model for autoimmune uveitis in man, extended the role of septin 7 to a potential key player in autoimmunity. Here, we revealed novel insights into septin 7 function by identification of DOCK8 as an interaction partner in primary blood-derived lymphocytes. Since DOCK8 is associated with important immune functions, our finding of significantly decreased DOCK8 expression and altered DOCK8 interaction network in ERU might explain changes in immune response and shows the contribution of DOCK8 in pathomechanisms of spontaneous autoimmune diseases. Moreover, our analyses revealed insights in DOCK8 function, by identifying the signal transducer ILK as a DOCK8 interactor in lymphocytes. Our finding of the enhanced enrichment of ILK in ERU cases indicates a deviant influence of DOCK8 on inter- and intracellular signaling in autoimmune disease.

immunology↗