pDCs Take a Deep Breath to Fight Viruses

Berod, Luciana; Sparwasser, Tim

doi:10.1016/j.immuni.2016.06.005

Cited by 3 publications

(5 citation statements)

References 10 publications

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“…Altogether, our results establish that pDCs regulate cross-presentation through the regulation of their phagosomal pH. In contrast to cDCs, the ROS involved in this process are generated by the mitochondrial respiratory chain, confirming that pDCs use different metabolic pathways from cDCs to support their specialized functions 43 .…”

Section: Discussionsupporting

confidence: 60%

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Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells

et al. 2018

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Cross-presentation allows exogenous antigen presentation in association with major histocompatibility complex class I molecules, a process crucial for the priming of CD8+ T-cell responses against viruses and tumors. By contrast to conventional dendritic cells (cDC), which cross-present antigens in the steady state, plasmacytoid dendritic cells (pDC) acquire this ability only after stimulation by Toll-like receptor (TLR) ligands. The intracellular pathways accounting for this functional difference are still unknown. Here we show that the induction of cross-presentation by pDCs is regulated by mitochondria through a reactive oxygen species (ROS)-dependent mechanism, involving pH alkalization and antigen protection. The reduction of mitochondrial ROS production dramatically decreases the cross-presentation capacity of pDCs, leading to a strong reduction of their capacity to trigger CD8+ T-cell responses. Our results demonstrate the importance of mitochondrial metabolism in pDC biology, particularly for the induction of adaptive immune responses.

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Section: Discussionsupporting

confidence: 60%

“…However, recent studies demonstrate that after activation, pDCs use mitochondrial respiration, through an autocrine I-IFN receptor-dependent pathway while cDCs increase glycolysis 39 , 43 . Interestingly, in this process, I-IFN promotes oxidative phosphorylation, which is required for full pDC activation.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells

et al. 2018

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“…[75]. A new study argues that upon activation, both pDCs and cDCs upregulate OXPHOS via an induction of fatty acid oxidation in a type I interferon-dependent manner [81,82]. Since these findings contradict previous reports [82] this process needs to be studied in further detail.…”

Section: Endogenous Metabolites and Metabolic Processes In Dcsmentioning

confidence: 83%

Metabolites: deciphering the molecular language between DCs and their environment

et al. 2016

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Dendritic cells (DCs) determine the outcome of the immune response based on signals they receive from the environment. Presentation of antigen under various contexts can lead to activation and differentiation of T cells for immunity or dampening of immune responses by establishing tolerance, primarily through the priming of regulatory T cells. Infections, inflammation and normal cellular interactions shape DC responses through direct contact or via cytokine signaling. Although it is widely accepted that DCs sense microbial components through pattern recognition receptors (PRRs), increasing evidence advocates for the existence of a set of signals that can profoundly shape DC function via PRR-independent pathways. This diverse group of host- or commensal-derived metabolites represents a newly appreciated code from which DCs can interpret environmental cues. In this review, we discuss the existing information on the effect of some of the most studied metabolites on DC function, together with the implications this may have in immune-mediated diseases.

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“…International Publisher functionalized phenotypes that constitute a wide-ranging immune surveillance [12,13], including conventional DC (cDCs) [14][15][16][17], Langerhans cells (LCs) [16,17], plasmacytoid DCs (pDCs) [18], and monocyte-derived DCs (mo-DCs) [19]; 2) rapid sensing and chemotaxis toward sites under the "non-self" invasion [20]; 3) diverse endocytic receptor repertoires and Ag process systems for multidimensional activation of T cells [21,22]; and 4) homing toward the secondary lymphoid organs (SLOs, including lymph nodes (LNs), spleen, Peyer's patches (PPs), adenoids and tonsils) during maturation to provide a timely integration of environmental signals. Moreover, besides direct capture of peripheral Ag [23][24][25][26], DCs are capable of collecting antigenic information from Ag-exposed live cells including non-leukocytes and other types or individuals of APCs [14,23,[27][28][29], serving as Ag acceptors to ensure an all-round supervision over the body and promote the flexible modulation of immune activation [1] and tolerance [30].…”

Section: Ivyspringmentioning

confidence: 99%

“…On the other hand, inflammatory signals induce the LNs-homing of migratory cDC1 and its subsequent Ag transfer to LNs-resident DCs through tight synaptic interaction [15], which facilitates the accumulation of Ag in LNs-resident DCs for activation of specific effector CD8 + T cells [1]. pDCs, formerly known as natural interferon producing cells (NIPCs), are the main producers of type I Interferon (IFN) [18] and play a key role in antiviral immunity. Although the capability of pDCs to generate in vivo cross-primed CD8 + T cells remains controversial, they have been shown to transfer antigen (possibly Ag protein, peptide, or p-MHC I [133]) to the bystander cDCs via EVs, which leads to efficient cross-priming of naive CD8 + T cells and induction of durable immunity.…”

Section: Dcs and Dcsmentioning

confidence: 99%

Antigen transfer and its effect on vaccine-induced immune amplification and tolerance

Shi¹,

Lu²,

You³

2022

Theranostics

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Antigen transfer refers to the process of intercellular information exchange, where antigenic components including nucleic acids, antigen proteins/peptides and peptide-major histocompatibility complexes (p-MHCs) are transmitted from donor cells to recipient cells at the thymus, secondary lymphoid organs (SLOs), intestine, allergic sites, allografts, pathological lesions and vaccine injection sites via trogocytosis, gap junctions, tunnel nanotubes (TNTs), or extracellular vesicles (EVs). In the context of vaccine inoculation, antigen transfer is manipulated by the vaccine type and administration route, which consequently influences, even alters the immunological outcome, i.e., immune amplification and tolerance. Mainly focused on dendritic cells (DCs)-based antigen receptors, this review systematically introduces the biological process, molecular basis and clinical manifestation of antigen transfer.

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pDCs Take a Deep Breath to Fight Viruses

Abstract: Conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) serve non-overlapping functions in immune responses. In this issue of Immunity, Pearce and colleagues (2016) report that pDCs use different metabolic pathways from cDCs to support their specialized function.

Cited by 3 publications

References 10 publications

Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells

Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells

Metabolites: deciphering the molecular language between DCs and their environment

Antigen transfer and its effect on vaccine-induced immune amplification and tolerance

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