scholarly journals Non-Pathogenic Mopeia Virus Induces More Robust Activation of Plasmacytoid Dendritic Cells than Lassa Virus

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 287 ◽  
Author(s):  
Justine Schaeffer ◽  
Stéphanie Reynard ◽  
Xavier Carnec ◽  
Natalia Pietrosemoli ◽  
Marie-Agnès Dillies ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Plasmacytoid Dendritic Cells ◽  
Health Concern ◽  
Lassa Virus ◽  
Type I ◽  
Viral Haemorrhagic Fever

Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of plasmacytoid dendritic cells (pDC) to LASV, as they are an important and early source of IFN-I. We compared the response of primary human pDCs to LASV and Mopeia virus (MOPV), which is very closely related to LASV, but non-pathogenic. We showed that pDCs are not productively infected by either MOPV or LASV, but produce IFN-I. However, the activation of pDCs was more robust in response to MOPV than LASV. In vivo, pDC activation may support the control of viral replication through IFN-I production, but also improve the induction of a global immune response. Therefore, pDC activation could play a role in the control of LASV infection.

scholarly journals Plasmacytoid Dendritic Cells Take Up Opsonized Antigen Leading to CD4+and CD8+T Cell Activation In Vivo

2008 ◽  
Vol 181 (6) ◽  
pp. 3811-3817 ◽  
Author(s):  
Pia Björck ◽  
Andreas Beilhack ◽  
Edward I. Herman ◽  
Robert S. Negrin ◽  
Edgar G. Engleman
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Plasmacytoid Dendritic Cells

scholarly journals Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonios Psarras ◽  
Adewonuola Alase ◽  
Agne Antanaviciute ◽  
Ian M. Carr ◽  
Md Yuzaiful Md Yusof ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Type I Interferon ◽  
Connective Tissue Diseases ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Interferon Production ◽  
Interferon Signature

AbstractAutoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have a crucial role in the progression to established autoimmune diseases. The cellular source and regulation in disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells have been thought to contribute to excessive type I interferon production. Here, we show that in preclinical autoimmunity and established systemic lupus erythematosus, plasmacytoid dendritic cells are not effector cells, have lost capacity for Toll-like-receptor-mediated cytokine production and do not induce T cell activation, independent of disease activity and the blood interferon signature. In addition, plasmacytoid dendritic cells have a transcriptional signature indicative of cellular stress and senescence accompanied by increased telomere erosion. In preclinical autoimmunity, we show a marked enrichment of an interferon signature in the skin without infiltrating immune cells, but with interferon-κ production by keratinocytes. In conclusion, non-hematopoietic cellular sources, rather than plasmacytoid dendritic cells, are responsible for interferon production prior to clinical autoimmunity.

scholarly journals Plasmacytoid dendritic cells are functionally exhausted while non-haematopoietic sources of type I interferon dominate human autoimmunity

2018 ◽  
Author(s):  
Antonios Psarras ◽  
Adewonuola Alase ◽  
Agne Antanaviciute ◽  
Ian M. Carr ◽  
Md Yuzaiful Md Yusof ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell Activation ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Connective Tissue Diseases ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Effector Cells ◽  
Transcriptional Signature

ABSTRACTAutoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons (IFNs) have a crucial role in the progression to established autoimmune diseases such as systemic lupus erythematosus (SLE). However, their cellular source and regulation in disease initiation are unclear. The current paradigm suggests that plasmacytoid dendritic cells (pDCs) are activated in SLE contributing to excessive IFN production. Here, we show that in preclinical autoimmunity, established SLE, and primary Sjögren’s Syndrome, pDCs are not effector cells, but rather have lost their capacity for TLR-mediated IFN-α and TNF production and fail to induce T cell activation, independently of disease activity and blood IFN signature. In addition, pDCs present a transcriptional signature of cellular stress and senescence accompanied by increased telomere erosion. Instead, we demonstrate a marked enrichment of IFN signature in non-lesional skin in preclinical autoimmunity. In these individuals and SLE patients, type I IFNs were abundantly produced by keratinocytes in the absence of infiltrating leucocytes. These findings revise our understanding of the role of IFN in the initiation of human autoimmunity, with non-haematopoietic tissues perpetuating IFN responses, which in turn predict clinical disease. These data indicate potential therapeutic targets outside the conventional immune system for treatment and prevention.

scholarly journals Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88

2007 ◽  
Vol 82 (1) ◽  
pp. 196-206 ◽  
Author(s):  
Andreas Jung ◽  
Hiroki Kato ◽  
Yutaro Kumagai ◽  
Himanshu Kumar ◽  
Taro Kawai ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Intracellular Signaling ◽  
Plasmacytoid Dendritic Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Type I ◽  
Ctl Response ◽  
Type I Ifns ◽  
Lcmv Infection

ABSTRACTToll-like receptors (TLRs) and retinoic acid-inducible gene I-like helicases (RLHs) are two major machineries recognizing RNA virus infection of innate immune cells. Intracellular signaling for TLRs and RLHs is mediated by their cytoplasmic adaptors, i.e., MyD88 or TRIF and IPS-1, respectively. In the present study, we investigated the contributions of TLRs and RLHs to the cytotoxic T-lymphocyte (CTL) response by using lymphocytoid choriomeningitis virus (LCMV) as a model virus. The generation of virus-specific cytotoxic T lymphocytes was critically dependent on MyD88 but not on IPS-1. Type I interferons (IFNs) are known to be important for the development of the CTL response to LCMV infection. Serum levels of type I IFNs and proinflammatory cytokines were mainly dependent on the presence of MyD88, although IPS-1−/−mice showed a decrease in IFN-α levels but not in IFN-β and proinflammatory cytokine levels. Analysis ofIfna6+/GFPreporter mice revealed that plasmacytoid dendritic cells (DCs) are the major source of IFN-α in LCMV infection. MyD88−/−mice were highly susceptible to LCMV infection in vivo. These results suggest that recognition of LCMV by plasmacytoid DCs via TLRs is responsible for the production of type I IFNs in vivo. Furthermore, the activation of a MyD88-dependent innate mechanism induces a CTL response, which eventually leads to virus elimination.

scholarly journals Response of the Splenic Dendritic Cell Population to Malaria Infection

2004 ◽  
Vol 72 (7) ◽  
pp. 4233-4239 ◽  
Author(s):  
Andrew L. Leisewitz ◽  
Kirk A. Rockett ◽  
Bonginkosi Gumede ◽  
Margaret Jones ◽  
Britta Urban ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Population ◽  
T Cell Activation ◽  
Malaria Infection ◽  
Cell Activation ◽  
Splenic Dendritic Cell ◽  
Dendritic Cell Population

ABSTRACT Dendritic cells, particularly those residing in the spleen, are thought to orchestrate acquired immunity to malaria, but it is not known how the splenic dendritic cell population responds to malaria infection and how this response compares with the responses of other antigen-presenting cells. We investigated this question for Plasmodium chabaudi AS infection in C57BL/6 mice. We found that dendritic cells, defined here by the CD11c marker, migrated from the marginal zone of the spleen into the CD4+ T-cell area within 5 days after parasites entered the bloodstream. This contrasted with the results observed for the macrophage and B-cell populations, which expanded greatly but did not show any comparable migration. Over the same time period dendritic cells showed upregulation of CD40, CD54, and CD86 costimulatory molecules that are required for successful T-cell activation. In dendritic cells, the peak intracellular gamma interferon expression (as shown by fluorescence-activated cell sorting) was on day 5, 2 days earlier than the peak expression in B-cells or macrophages. These findings show that splenic dendritic cells are actively engaged in the earliest phase of malarial infection in vivo and are likely to be critical in shaping the subsequent immune response.

scholarly journals Type I Interferon Inhibition and Dendritic Cell Activation during Gammaherpesvirus Respiratory Infection

2007 ◽  
Vol 81 (18) ◽  
pp. 9778-9789 ◽  
Author(s):  
Janet L. Weslow-Schmidt ◽  
Nancy A. Jewell ◽  
Sara E. Mertz ◽  
J. Pedro Simas ◽  
Joan E. Durbin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
The Body ◽  
Type I ◽  
Type I Ifn ◽  
Dendritic Cell Activation ◽  
Murine Gammaherpesvirus

ABSTRACT The respiratory tract is a major mucosal site for microorganism entry into the body, and type I interferon (IFN) and dendritic cells constitute a first line of defense against viral infections. We have analyzed the interaction between a model DNA virus, plasmacytoid dendritic cells, and type I IFN during lung infection of mice. Our data show that murine gammaherpesvirus 68 (γHV68) inhibits type I IFN secretion by dendritic cells and that plasmacytoid dendritic cells are necessary for conventional dendritic cell maturation in response to γHV68. Following γHV68 intranasal inoculation, the local and systemic IFN-α/β response is below detectable levels, and plasmacytoid dendritic cells are activated and recruited into the lung with a tissue distribution that differs from that of conventional dendritic cells. Our results suggest that plasmacytoid dendritic cells and type I IFN have important but independent roles during the early response to a respiratory γHV68 infection. γHV68 infection inhibits type I IFN production by dendritic cells and is a poor inducer of IFN-α/β in vivo, which may serve as an immune evasion strategy.

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

scholarly journals Acidosis-Induced TGF-β2 Production Promotes Lipid Droplet Formation in Dendritic Cells and Alters Their Potential to Support Anti-Mesothelioma T Cell Response

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1284
Author(s):  
Natalia Trempolec ◽  
Charline Degavre ◽  
Bastien Doix ◽  
Davide Brusa ◽  
Cyril Corbet ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lipid Droplet ◽  
T Cell Activation ◽  
Cell Response ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
T Cell Response ◽  
Mesenchymal Transition

For poorly immunogenic tumors such as mesothelioma there is an imperious need to understand why antigen-presenting cells such as dendritic cells (DCs) are not prone to supporting the anticancer T cell response. The tumor microenvironment (TME) is thought to be a major contributor to this DC dysfunction. We have reported that the acidic TME component promotes lipid droplet (LD) formation together with epithelial-to-mesenchymal transition in cancer cells through autocrine transforming growth factor-β2 (TGF-β2) signaling. Since TGF-β is also a master regulator of immune tolerance, we have here examined whether acidosis can impede immunostimulatory DC activity. We have found that exposure of mesothelioma cells to acidosis promotes TGF-β2 secretion, which in turn leads to LD accumulation and profound metabolic rewiring in DCs. We have further documented how DCs exposed to the mesothelioma acidic milieu make the anticancer vaccine less efficient in vivo, with a reduced extent of both DC migratory potential and T cell activation. Interestingly, inhibition of TGF-β2 signaling and diacylglycerol O-acyltransferase (DGAT), the last enzyme involved in triglyceride synthesis, led to a significant restoration of DC activity and anticancer immune response. In conclusion, our study has identified that acidic mesothelioma milieu drives DC dysfunction and altered T cell response through pharmacologically reversible TGF-β2-dependent mechanisms.

scholarly journals Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo

2005 ◽  
Vol 174 (8) ◽  
pp. 4696-4705 ◽  
Author(s):  
Jelena S. Bezbradica ◽  
Aleksandar K. Stanic ◽  
Naoto Matsuki ◽  
Helene Bour-Jordan ◽  
Jeffrey A. Bluestone ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation
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