PMID- 25806537
OWN - NLM
STAT- MEDLINE
DCOM- 20160303
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Enterovirus-infected beta-cells induce distinct response patterns in BDCA1+ and 
      BDCA3+ human dendritic cells.
PG  - e0121670
LID - 10.1371/journal.pone.0121670 [doi]
LID - e0121670
AB  - Enteroviruses often cause mild disease, yet are also linked to development of 
      autoimmune diabetes. Dendritic cells (DCs) shape both innate and adaptive immune 
      responses, including anti-viral responses. How different human DC subsets shape 
      anti-viral responses, whether they have complementary or overlapping functions 
      and how this relates to autoimmune responses is largely unknown. We used 
      enterovirus-infected beta-cells and freshly isolated human myeloid DC (mDC) subsets 
      as a model for autoimmune type 1 diabetes. Our data show that both the BDCA1+ and 
      BDCA3+ mDC subsets engulf mock- as well as virus-infected beta-cells, albeit BDCA1+ 
      mDCs are more efficient. Uptake of enterovirus-infected, but not mock-infected 
      cells, activated both DC subsets as indicated by the induction of co-stimulatory 
      molecules and secretion of type I and type III interferons. Both subsets produced 
      similar amounts of interferon-alpha, yet the BDCA3+ DC were superior in IFN-lambda 
      production. The BDCA1+ mDCs more strongly upregulated PD-L1, and were superior in 
      IL-12 and IL-10 production as compared to the BDCA3+ DC. Despite lack of IL-12 
      production by the BDCA3+ DC, both BDCA1+ and BDCA3+ DCs activated T cells in 
      allogeneic mixed lymphocyte reaction towards a Th1-type reactivity while 
      suppressing Th2-associated cytokines.
FAU - Schulte, Barbara M
AU  - Schulte BM
AD  - Department of Tumor Immunology, Radboud university medical center, Radboud 
      Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
FAU - Gielen, Paul R
AU  - Gielen PR
AD  - Department of Tumor Immunology, Radboud university medical center, Radboud 
      Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
FAU - Kers-Rebel, Esther D
AU  - Kers-Rebel ED
AD  - Department of Tumor Immunology, Radboud university medical center, Radboud 
      Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
FAU - Schreibelt, Gerty
AU  - Schreibelt G
AD  - Department of Tumor Immunology, Radboud university medical center, Radboud 
      Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
FAU - van Kuppeveld, Frank J M
AU  - van Kuppeveld FJ
AD  - Virology Division, Department of Infectious Diseases and Immunology, Faculty of 
      Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
FAU - Adema, Gosse J
AU  - Adema GJ
AD  - Department of Tumor Immunology, Radboud university medical center, Radboud 
      Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150325
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Cell Line, Tumor
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Enterovirus/immunology
MH  - Humans
MH  - Insulin-Secreting Cells/*immunology/metabolism
MH  - Myeloid Cells/*immunology/metabolism
MH  - Rats
PMC - PMC4373773
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/26 06:00
MHDA- 2016/03/05 06:00
PMCR- 2015/03/25
CRDT- 2015/03/26 06:00
PHST- 2014/11/03 00:00 [received]
PHST- 2015/02/03 00:00 [accepted]
PHST- 2015/03/26 06:00 [entrez]
PHST- 2015/03/26 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
PHST- 2015/03/25 00:00 [pmc-release]
AID - PONE-D-14-47078 [pii]
AID - 10.1371/journal.pone.0121670 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 25;10(3):e0121670. doi: 10.1371/journal.pone.0121670. 
      eCollection 2015.