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The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4

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In this study, we show that Mycobacterium avium subsp. paratuberculosis MAP1305 induces the maturation of bonemarrow-derived dendritic cells (BMDCs), a representativeantigen presenting cell (APC). MAP1305 protein induces DCmaturation and the production of pro-inflammatory cytokines(Interleukin (IL)-6), tumor necrosis factor (TNF)-α, and IL-1β)through Toll like receptor-4 (TLR-4) signaling by directly bindingwith TLR4. MAP1305 activates the phosphorylation of MAPKs,such as ERK, p38MAPK, and JNK, which is essential for DCmaturation. Furthermore, MAP1305-treated DCs transform naïveT cells to polarized CD4+ and CD8+ T cells, thus indicating akey role for this protein in the Th1 polarization of the resultingimmune response. Taken together, M. avium subsp. paratuberculosisMAP1305 is important for the regulation of innateimmune response through DC-mediated proliferation of CD4+and CD8+ T cells.

Abstract

In this study, we show that Mycobacterium avium subsp. paratuberculosis MAP1305 induces the maturation of bonemarrow-derived dendritic cells (BMDCs), a representativeantigen presenting cell (APC). MAP1305 protein induces DCmaturation and the production of pro-inflammatory cytokines(Interleukin (IL)-6), tumor necrosis factor (TNF)-α, and IL-1β)through Toll like receptor-4 (TLR-4) signaling by directly bindingwith TLR4. MAP1305 activates the phosphorylation of MAPKs,such as ERK, p38MAPK, and JNK, which is essential for DCmaturation. Furthermore, MAP1305-treated DCs transform naïveT cells to polarized CD4+ and CD8+ T cells, thus indicating akey role for this protein in the Th1 polarization of the resultingimmune response. Taken together, M. avium subsp. paratuberculosisMAP1305 is important for the regulation of innateimmune response through DC-mediated proliferation of CD4+and CD8+ T cells.

참고문헌 (23)

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