ABSTRACTA lack of appropriate disease models has limited our understanding of the pathogenesis of persistent enteric infections withMycobacterium aviumsubsp.paratuberculosis. A model was developed for the controlled delivery of a defined dose ofM. aviumsubsp.paratuberculosisto surgically isolated ileal segments in newborn calves. The stable intestinal segments enabled the characterization of host responses to persistentM. aviumsubsp.paratuberculosisinfections after a 9-month period, including an analysis of local mucosal immune responses relative to an adjacent uninfected intestinal compartment.M. aviumsubsp.paratuberculosisremained localized at the initial site of intestinal infection and was not detected by PCR in the mesenteric lymph node.M. aviumsubsp.paratuberculosis-specific T cell proliferative responses included both CD4 and γδ T cell receptor (γδTcR) T cell responses in the draining mesenteric lymph node. The levels of CD8+and γδTcR+T cells increased significantly (P< 0.05) in the lamina propria, andM. aviumsubsp.paratuberculosis-specific tumor necrosis factor alpha (TNF-α) and gamma interferon secretion by lamina propria leukocytes was also significantly (P< 0.05) increased. There was a significant (P< 0.05) accumulation of macrophages and dendritic cells (DCs) in the lamina propria, but the expression of mucosal toll-like receptors 1 through 10 was not significantly changed byM. aviumsubsp.paratuberculosisinfection. In conclusion, surgically isolated ileal segments provided a model system for the establishment of a persistent and localized entericM. aviumsubsp.paratuberculosisinfection in cattle and facilitated the analysis ofM. aviumsubsp.paratuberculosis-specific changes in mucosal leukocyte phenotype and function. The accumulation of DC subpopulations in the lamina propria suggests that further investigation of mucosal DCs may provide insight into host responses toM. aviumsubsp.paratuberculosisinfection and improve vaccine strategies to preventM. aviumsubsp.paratuberculosisinfection.
Thermal injury-plus-sepsis contributes to a substantial deletion of intestinal mesenteric lymph node CD4+ T cell via apoptosis
