Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells

Abstract

Plasmacytoid dendritic cells (pDC) produce type I interferon (IFN-I) in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid-binding immunoglobulin-like lectin that has an immunomodulatory role during viral infections. Here, 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 or not. We also examined the expression pattern of SiglecH in this study. We observed that SiglecH was expressed by specialized macrophages and progenitors of classical DC (cDC) and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH-DTR Tg mice but not CLEC4C-DTR Tg mice after diphtheria toxin (DT) treatment. Using two different 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 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.

Transcriptional Control of Dendritic Cell Development

“…This study reported a greater impact of pDC deletion compared with the two other studies (67, 68), suggesting that pDCs were required for inflammation induced by TLR stimulation and bacterial and viral infections, as well as for controlling both CD4 + T cell responses and CD8 + T cell responses. The discrepancy between these findings and results of other approaches deleting pDCs may derive from the expression of Siglec-H on progenitors that affect other subsets of DCs (70), as discussed below. Thus, deletion of Siglec-H + progenitors would cause a reduction in more than pDCs, and would likely reduce cDC development as well, potentially explaining the relatively larger phenotype reported by these authors.…”

Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

“…Deletion of SiglecH, the only murine receptor known so far, did not cause overt autoimmune or inflammatory diseases. SiglecH-deficient mice show higher IFN response to murine cytomegalovirus (MCMV), whereas other immune pheno-types in these mice are not pDC-intrinsic (Puttur et al, 2013; Swiecki et al, 2014). We found that Ptprs reduction or DC-specific deletion on Ptprf null background caused mild spontaneous colitis that could be transferred with hematopoietic cells.…”

The multifaceted biology of plasmacytoid dendritic cells

“…However, specialized macrophage subsets in the spleen, lymph nodes and brain also express SIGLEC-H 17,19 . In addition, studies in reporter mice have confirmed Siglech mRNA transcription in progenitor cells 18,20,21 . Mouse pDCs can also express CD8α and, like human pDCs, CD4.…”