BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAM CD11b Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming

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The arrival of bacilli in the lymph node is a bottleneck for initiating T cell responses to mycobacteria but remains poorly studied. To address this we used a mouse model to track the entry of cells and bacteria into the lymph node during skin infection with Mycobacterium bovis BCG, the live tuberculosis vaccine. We identified a population of migratory Dendritic cells that transport bacilli from the skin into the lymph node and which engage CD4+ T cells therein. The mobilization of Dendritic cells from the skin, and with these cells the transport of mycobacteria into the lymph node, was regulated by cytokines, in particular Interleukin–1. This was also dependent on MyD88, an adaptor molecule downstream of the Interleukin–1 receptor. We also found a requirement for MyD88 in driving Dendritic cells to the lymph node that was both inherent and extrinsic to the migrating cell. These findings bare consequences for our understanding of how T-cell responses are initiated during microbial challenge in the skin and hold promises for improving vaccines of low-to-modest efficacy such as BCG, which rely on such responses.

Vyšlo v časopise: BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAM CD11b Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005206
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005206

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