Type I interferon dependence of plasmacytoid dendritic cell activation and migration

Abstract

Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration.

Self‐priming determines high type I IFN production by plasmacytoid dendritic cells

“…As such, we assume that pDC accumulation in lymphoid tissue represents the physiological correlate of the in vitro observed cluster formation, thereby providing the prerequisite for the positive type I IFN feedforward loop described here. This is in line with reports demonstrating that type I IFN activity is critical for murine pDC activation in vitro and in vivo [16,17], while pDCs are capable of an IFNAR-independent, early, yet weak IFN-α response [18]. However, it has also been noted that other studies have reported that pDCs do not require functional IFNAR signaling to exert type I IFN production themselves [19,20].…”

Visualization of IFNβ production by plasmacytoid versus conventional dendritic cells under specific stimulation conditions in vivo

“…The in vivo relocalization of YFP ϩ cells from the red pulp via the marginal zone to the T cell area at Ϸ24 h after poly(I:C) stimulation is delayed, compared with the general redistribution of DCs after LPS treatment, where they are found in the splenic T cell zone by 6 h after injection (29). Interestingly, after injection of CpG ODN, YFP ϩ pDCs localized to the splenic T and B cell zones, whereas pDCs as a whole were described before to cluster mostly in the marginal zone with only few cells present in the splenic T cell areas (30). Taking these two independent observations into account, our data argue for a specialized migration pattern of IFN␤-expressing cells within the subpopulation of activated pDCs in response to activation with selective molecular patterns representative of different types of pathogens.…”

Type I interferon regulates pDC maturation and Ly49Q expression

“…However, it has been reported that CCR7 expression is up-regulated on pDC in response to pathogenic stimuli, and that pDC migrate to the CCR7 ligands CCL19 and CCL21 expressed by stromal cells in the T cell zone and in HEV [29,50,51]. Moreover, TLR signals or type I IFN affect pDC migration via CXCR3L and CCR7 ligand induction [16,17]. Thus, IFN signaling in response to poly(I:C) stimulation might up-regulate these chemokine receptors on Ly49Q -pDC, allowing them to migrate into the periphery.…”

“…Zuniga et al [15] recently showed that type I IFN negatively regulate pDC maturation during viral infection, and others [16] have reported that IFN control chemokine expression patterns that lead pDC to inflamed lymph nodes [17].…”