|LAWS, ELIZABETH - Washington State University|
|CARDIERI, MARIA - Washington State University|
|SOUZA, CLEVERSON - Washington State University|
Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/4/2015
Publication Date: 6/15/2015
Citation: Bannantine, J.P., Stabel, J.R., Laws, E., Cardieri, M.C., Souza, C. 2015. Mycobacterium avium subspecies paratuberculosis recombinant proteins modulate antimycobacterial functions of bovine macrophages. PLoS One. doi: 10.1371/journal.pone.0128966.
Interpretive Summary: Despite efforts on the part of the largest dairy states to implement control programs that include vaccination or indemnity for farmers to get rid of infected cattle, Johne’s disease has been gradually increasing over time in the U.S. and elsewhere. Thus additional research is needed, especially to better understand the infection process for vaccination strategies and improved diagnostic tests for informed herd management. This work focused on the former, by examining how the cattle immune response handles specific M. avium subspecies paratuberculosis (the bacterium that causes Johne’s disease) proteins. We discovered that some proteins, termed lipoproteins, activate a cow’s kinase pathway, which helps the bacteria survive longer in the cow. Now that we have identified these proteins, we have vaccine targets. This research is of primary interest to veterinarians, stakeholders and other researchers in the field.
Technical Abstract: It has been shown that Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) activates the Mitogen Activated Protein Kinase (MAPK) p38 pathway, yet it is unclear which components of M. paratuberculosis are involved in the process. Therefore, a set of 42 M. paratuberculosis recombinant proteins expressed from coding sequences annotated as lipoproteins were screened for their ability to induce IL-10 expression, an indicator of MAPK-p38 activation in bovine monocyte-derived macrophages. A lipoprotein, designated as MAP3837c, was among a group of 6 proteins that strongly induced IL-10 gene transcription in bovine macrophages, averaging a 3.1-fold increase compared to non-stimulated macrophages. However, a parallel increase in expression of IL-12 and TNF-alpha was only observed in macrophages exposed to a subset of these 6 proteins. Selected lipoproteins were further analyzed for their ability to enhance survival of M. avium within bovine macrophages as measured by recovered viable bacteria and nitrite production. MAP0261c, MAP1604c, and MAP3837c along with M. paratuberculosis significantly enhanced phosphorylation of MAPK-p38 in bovine macrophages. Collectively, these data identify M. paratuberculosis proteins that play a role in survival within bovine macrophages.