PMID- 26440518
OWN - NLM
STAT- MEDLINE
DCOM- 20160429
LR  - 20190202
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 11
IP  - 10
DP  - 2015 Oct
TI  - BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh 
      Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming.
PG  - e1005206
LID - 10.1371/journal.ppat.1005206 [doi]
LID - e1005206
AB  - 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-Guerin (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.
FAU - Bollampalli, Vishnu Priya
AU  - Bollampalli VP
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Harumi Yamashiro, Livia
AU  - Harumi Yamashiro L
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden; Department of Pharmacology, Federal University of Santa 
      Catarina, Florianopolis, Brazil.
FAU - Feng, Xiaogang
AU  - Feng X
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Bierschenk, Damien
AU  - Bierschenk D
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Gao, Yu
AU  - Gao Y
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Blom, Hans
AU  - Blom H
AD  - Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden.
FAU - Henriques-Normark, Birgitta
AU  - Henriques-Normark B
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Nylen, Susanne
AU  - Nylen S
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Rothfuchs, Antonio Gigliotti
AU  - Rothfuchs AG
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151006
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (BCG Vaccine)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Interleukin-1)
SB  - IM
MH  - Animals
MH  - BCG Vaccine/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Movement/immunology
MH  - Dendritic Cells/*immunology/metabolism/microbiology
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - Lymph Nodes/*immunology
MH  - Lymphocyte Activation/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microscopy, Confocal
MH  - Mycobacterium bovis/immunology
MH  - Myeloid Differentiation Factor 88/immunology
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Interleukin-1/immunology
MH  - Skin/immunology/microbiology
MH  - Tuberculosis/immunology/prevention & control
PMC - PMC4594926
COIS- The authors have declared that no competing interests exist.
EDAT- 2015/10/07 06:00
MHDA- 2016/04/30 06:00
PMCR- 2015/10/06
CRDT- 2015/10/07 06:00
PHST- 2015/04/07 00:00 [received]
PHST- 2015/09/14 00:00 [accepted]
PHST- 2015/10/07 06:00 [entrez]
PHST- 2015/10/07 06:00 [pubmed]
PHST- 2016/04/30 06:00 [medline]
PHST- 2015/10/06 00:00 [pmc-release]
AID - PPATHOGENS-D-15-00825 [pii]
AID - 10.1371/journal.ppat.1005206 [doi]
PST - epublish
SO  - PLoS Pathog. 2015 Oct 6;11(10):e1005206. doi: 10.1371/journal.ppat.1005206. 
      eCollection 2015 Oct.