Cell depletion in mice that express diphtheria toxin receptor under the control of siglech encompasses more than plasmacytoid dendritic cells

Melissa Swiecki, Yaming Wang, Elena Riboldi, Alfred H J Kim, Amiran Dzutsev, Susan Gilfillan, William Vermi, Christiane Ruedl, Giorgio Trinchieri, Marco Colonna

Research output: Contribution to journalArticle

Abstract

Plasmacytoid dendritic cells (pDC) produce IFN-I in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid-binding Ig-like lectin that has an immunomodulatory role during viral infections. In this study, we evaluated the impact of SiglecH deficiency on cytokine responses in the presence and absence of pDC. We found that lack of SiglecH enhanced IFN-I responses to viral infection, regardless of whether pDC were depleted. We also examined the expression pattern of SiglecH and observed that it was expressed by specialized macrophages and progenitors of classical dendritic cells and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH-diphtheria toxin receptor (DTR)-transgenic (Tg) mice but not in CLEC4C-DTR-Tg mice after diphtheria toxin (DT) treatment. Using two bacterial models, we found that SiglecH-DTR-Tg mice injected with DT had altered bacterial uptake and were more susceptible to lethal Listeria monocytogenes infection than were DT-treated CLEC4C-DTR-Tg mice. Taken together, our findings suggest that lack of SiglecH may affect cytokine responses by cell types other than pDC during viral infections, perhaps by altering viral distribution or burden, and that cell depletion in SiglecH-DTR-Tg mice encompasses more than pDC. The Journal of Immunology, 2014, 192: 4409-4416.

Original languageEnglish
Pages (from-to)4409-4416
Number of pages8
JournalJournal of Immunology
Volume192
Issue number9
DOIs
Publication statusPublished - May 1 2014

ASJC Scopus subject areas

  • Immunology

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    Swiecki, M., Wang, Y., Riboldi, E., Kim, A. H. J., Dzutsev, A., Gilfillan, S., Vermi, W., Ruedl, C., Trinchieri, G., & Colonna, M. (2014). Cell depletion in mice that express diphtheria toxin receptor under the control of siglech encompasses more than plasmacytoid dendritic cells. Journal of Immunology, 192(9), 4409-4416. https://doi.org/10.4049/jimmunol.1303135