Host Responses to Persistent Mycobacterium avium SubspeciesparatuberculosisInfection in Surgically Isolated Bovine Ileal Segments

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.

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Influences of orally administered lactoferrin on IFN-γ and IL-10 production by intestinal intraepithelial lymphocytes and mesenteric lymph-node cellsThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

Biochemistry and Cell Biology ◽

10.1139/o06-056 ◽

2006 ◽

Vol 84 (3) ◽

pp. 363-368 ◽

Cited By ~ 30

Author(s):

Natsuko Takakura ◽

Hiroyuki Wakabayashi ◽

Koji Yamauchi ◽

Mitsunori Takase

Keyword(s):

Lymph Node ◽

T Cell ◽

T Cell Receptor ◽

Mesenteric Lymph Node ◽

Cell Receptor ◽

Intraepithelial Lymphocytes ◽

Bovine Lactoferrin ◽

Intestinal Intraepithelial Lymphocytes ◽

Mesenteric Lymph ◽

Ifn Γ

Intestinal mucosal immunity plays an important role in mucosal and systemic immune responses. We investigated the influences of orally administered bovine lactoferrin (LF) on cytokine production by intestinal intraepithelial lymphocytes (IEL) and mesenteric lymph-node (MLN) cells, especially T cells. Bovine LF or bovine serum albumin (control) was administered to mice once daily for 3 d. After 24 h from the last administration, IEL of the jejunum and ileum and MLN cells were isolated. These cells were cultured with and without the anti-T-cell-receptor antibody, and then the culture supernatants were assayed for cytokines with ELISA. Oral LF did not affect the ratio of T-cell subpopulations in IEL and MLN; however, LF enhanced both interferon (IFN)-γ and interleukin (IL)-10 production by unstimulated IEL and by IEL stimulated with the αβ T-cell receptor but not with the γδ T-cell receptor. LF also enhanced both IFN-γ and IL-10 production by stimulated and unstimulated MLN cells. The production level of IFN-γ by MLN cells was correlated with that of IL-10. These results suggest that oral LF enhances the production of both Th1-type and Th2/Tr-type cytokines in the small intestine of healthy animals.

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