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BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming
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2015 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 11, no 10, e1005206Article in journal (Refereed) PublishedText
Abstract [en]

The transport of antigen from the periphery to the draining lymph node (DLN) is critical for T-cell priming but remains poorly studied during infection with Mycobacterium bovis Bacille Calmette-Guérin (BCG). To address this we employed a mouse model to track the traffic of Dendritic cells (DCs) and mycobacteria from the BCG inoculation site in the skin to the DLN. Detection of BCG in the DLN was concomitant with the priming of antigen-specific CD4+ T cells at that site. We found EpCAMlow CD11bhigh migratory skin DCs to be mobilized during the transport of BCG to the DLN. Migratory skin DCs distributed to the T-cell area of the LN, co-localized with BCG and were found in close apposition to antigen-specific CD4+ T cells. Consequently, blockade of skin DC traffic into DLN dramatically reduced mycobacterial entry into DLN and muted T-cell priming. Interestingly, DC and mycobacterial entry into the DLN was dependent on IL-1R-I, MyD88, TNFR-I and IL-12p40. In addition, we found using DC adoptive transfers that the requirement for MyD88 in BCG-triggered migration was not restricted to the migrating DC itself and that hematopoietic expression of MyD88 was needed in part for full-fledged migration. Our observations thus identify a population of DCs that contribute towards the priming of CD4+ T cells to BCG infection by transporting bacilli into the DLN in an IL-1R-MyD88-dependent manner and reveal both DC-intrinsic and -extrinsic requirements for MyD88 in DC migration.

Place, publisher, year, edition, pages
Public Library of Science , 2015. Vol. 11, no 10, e1005206
Keyword [en]
epithelial cell adhesion molecule, interleukin 1 receptor type I, interleukin 12, myeloid differentiation factor 88, tumor necrosis factor receptor, animal cell, animal experiment, animal model, Article, bacterial skin disease, CD4+ T lymphocyte, cell migration assay, confocal microscopy, controlled study, flow cytometry, immune response, microarray analysis, Mycobacterium bovis BCG, nonhuman, pathogenesis, protein expression, quantitative assay, reverse transcription polymerase chain reaction, satellite virus, T lymphocyte activation, transwell migration assay
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
URN: urn:nbn:se:kth:diva-181195DOI: 10.1371/journal.ppat.1005206ScopusID: 2-s2.0-84946040280OAI: diva2:900874

Funding Details: Stiftelsen Lars Hiertas Minne

QC 20160205

Available from: 2016-02-05 Created: 2016-01-29 Last updated: 2016-02-05Bibliographically approved

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Blom, Hans
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Cell PhysicsScience for Life Laboratory, SciLifeLab
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