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Enterovirus-Infected β-Cells Induce Distinct Response Patterns in BDCA1+ and BDCA3+ Human Dendritic Cells

Author

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  • Barbara M Schulte
  • Paul R Gielen
  • Esther D Kers-Rebel
  • Gerty Schreibelt
  • Frank J M van Kuppeveld
  • Gosse J Adema

Abstract

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 β-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 β-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-α, yet the BDCA3+ DC were superior in IFN-λ 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.

Suggested Citation

  • Barbara M Schulte & Paul R Gielen & Esther D Kers-Rebel & Gerty Schreibelt & Frank J M van Kuppeveld & Gosse J Adema, 2015. "Enterovirus-Infected β-Cells Induce Distinct Response Patterns in BDCA1+ and BDCA3+ Human Dendritic Cells," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-17, March.
    • Handle: RePEc:plo:pone00:0121670
    DOI: 10.1371/journal.pone.0121670
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    1. David Sancho & Olivier P. Joffre & Anna M. Keller & Neil C. Rogers & Dolores Martínez & Patricia Hernanz-Falcón & Ian Rosewell & Caetano Reis e Sousa, 2009. "Identification of a dendritic cell receptor that couples sensing of necrosis to immunity," Nature, Nature, vol. 458(7240), pages 899-903, April.
    2. Oliver Schulz & Sandra S. Diebold & Margaret Chen & Tanja I. Näslund & Martijn A. Nolte & Lena Alexopoulou & Yasu-Taka Azuma & Richard A. Flavell & Peter Liljeström & Caetano Reis e Sousa, 2005. "Toll-like receptor 3 promotes cross-priming to virus-infected cells," Nature, Nature, vol. 433(7028), pages 887-892, February.
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