Djaoud Z.,Etablissement Francais du Sang |
Djaoud Z.,University of Nantes |
Riou R.,Etablissement Francais du Sang |
Riou R.,University of Nantes |
And 14 more authors.
Journal of Innate Immunity | Year: 2016
Among innate cells, natural killer (NK) cells play a crucial role in the defense against cytomegalovirus (CMV). In some individuals, CMV infection induces the expansion of NKG2C+ NK cells that persist after control of the infection. We have previously shown that KIR2DL+ NK cells, in contrast to NKG2C+ NK cells, contribute to controlling CMV infection using a CMV-infected monocyte-derived dendritic cell (MDDC) model. However, the nature of CMV-infected cells contributing to the expansion of the NKG2C+ NK cell subset remains unclear. To gain more insight into this question, we investigated the contribution of NKG2C+ NK cell activation by CMV-infected primary human aortic endothelial cells (EC) isolated from kidney transplant donors, which constitutively express the human leukocyte antigen (HLA)-E molecule. Here, we show that, although classic HLA class I expression was drastically downregulated, nonclassic HLA-E expression was maintained in CMV-infected EC. By comparing HLA expression patterns in CMV-infected EC, fibroblasts and MDDC, we demonstrate a cell-dependent modulation of HLA-E expression by CMV infection. NKG2C+ NK cell degranulation was significantly triggered by CMV-infected EC regardless of the nature of the HLA-E allele product. EC, predominantly present in vessels, may constitute a privileged site for CMV infection that drives a 'memory' NKG2C+ NK cell subset. © 2016 S. Karger AG, Basel. Copyright: All rights reserved.
Rimbert M.,Nantes University Hospital Center |
Rimbert M.,Institute Of Transplantation Urologie Nephrologie Itun |
Rimbert M.,French Institute of Health and Medical Research |
Rimbert M.,University of Nantes |
And 17 more authors.
PLoS ONE | Year: 2011
Background: Dendritic cells (DC) and regulatory cells (Treg) play pivotal roles in controlling both normal and autoimmune adaptive immune responses. DC are the main antigen-presenting cells to T cells, and they also control Treg functions. In this study, we examined the frequency and phenotype of DC subsets, and the frequency and function of Treg from patients with ANCA-associated vasculitis (AAV). Methodology/Principal Findings: Blood samples from 19 untreated patients with AAV during flares and before any immunosuppressive treatment were analyzed, along with 15 AAV patients in remission and 18 age-matched healthy controls. DC and Treg numbers, and phenotypes were assessed by flow cytometry, and in vitro suppressive function of Treg was determined by co-culture assay. When compared to healthy volunteers, absolute numbers of conventional and plasmacytoid DC were decreased in AAV patients. During the acute phase this decrease was significantly more pronounced and was associated with an increased DC expression of CD62L. Absolute numbers of Treg (CD4+CD25highCD127low/- Tcells) were moderately decreased in patients. FOXP3 and CD39 were expressed at similar levels on Treg from patients as compared to controls. The suppressive function of Treg from AAV patients was dramatically decreased as compared to controls, and this defect was more pronounced during flares than remission. This Treg functional deficiency occurred in the absence of obvious Th17 deviation. Conclusion: In conclusion, these data show that AAV flares are associated with both a decrease number and altered phenotype of circulating DC and point to a role for Treg functional deficiency in the pathogenesis of AAV. © 2011 Rimbert et al.
Roquilly A.,University of Nantes |
Gautreau L.,Institute National Of La Sante Et Of La Recherche Me Dicale |
Segain J.P.,University of Nantes |
de Coppet P.,University of Nantes |
And 9 more authors.
PLoS ONE | Year: 2010
Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferonbeta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia. © 2010 Roquilly et al.
Corre P.,University of Nantes |
Merceron C.,University of Nantes |
Vignes C.,University of Nantes |
Sourice S.,University of Nantes |
And 10 more authors.
PLoS ONE | Year: 2013
Purpose: Autologous bone grafting (BG) remains the standard reconstruction strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials, such as biphasic calcium phosphate (BCP), do not yield consistent results when used alone and must then be combined with cells through bone tissue engineering (BTE). In this context, total bone marrow (TBM) and bone marrow-derived mesenchymal stem cells (MSC) are the primary sources of cellular material used with biomaterials. However, several other BTE strategies exist, including the use of growth factors, various scaffolds, and MSC isolated from different tissues. Thus, clinicians might be unsure as to which method offers patients the most benefit. For this reason, the aim of this study was to compare eight clinically relevant BTE methods in an ''all-in-one'' study. Methods: We used a transgenic rat strain expressing green fluorescent protein (GFP), from which BG, TBM, and MSC were harvested. Progenitor cells were then mixed with CaP materials and implanted subcutaneously into nude mice. After eight weeks, bone formation was evaluated by histology and scanning electron microscopy, and GFP-expressing cells were tracked with photon fluorescence microscopy. Results/Conclusions: Bone formation was observed in only four groups. These included CaP materials mixed with BG or TBM, in which abundant de novo bone was formed, and BCP mixed with committed cells grown in two- and threedimensions, which yielded limited bone formation. Fluorescence microscopy revealed that only the TBM and BG groups were positive for GFP expressing-cells, suggesting that these donor cells were still present in the host and contributed to the formation of bone. Since the TBM-based procedure does not require bone harvest or cell culture techniques, but provides abundant de novo bone formation, we recommend consideration of this strategy for clinical applications. © 2013 Corre et al.
Lelan F.,French Institute of Health and Medical Research |
Lelan F.,Institute Of Transplantation Urologie Nephrologie Itun |
Lelan F.,University of Nantes |
Lelan F.,Nantes University Hospital Center |
And 35 more authors.
Parkinson's Disease | Year: 2011
A transgenic Sprague Dawley rat bearing the A30P and A53T -synuclein (-syn) human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the human -syn mutations on the neuropathological events involved in the progression of the Parkinsons disease (PD). This rat displayed olfactory deficits in the absence of motor impairments as observed in most early PD cases. In order to investigate the role of the mutated -syn on cell proliferation, we focused on the subventricular zone (SVZ) and the olfactory bulbs (OB) as a change of the proliferation could affect OB function. The effect on OB dopaminergic innervation was investigated. The human -syn co-localized in TH-positive OB neurons. No human -syn was visualized in the SVZ. A significant increase in resident cell proliferation in the glomerular but not in the granular layers of the OB and in the SVZ was observed. TH innervation was significantly increased within the glomerular layer without an increase in the size of the glomeruli. Our rat could be a good model to investigate the role of human mutated -syn on the development of olfactory deficits. Copyright © 2011 Faustine Lelan et al.
Fakhouri F.,Nantes University Hospital Center |
Fakhouri F.,French Institute of Health and Medical Research |
Fakhouri F.,Institute Of Transplantation Urologie Nephrologie Itun
Nephrologie et Therapeutique | Year: 2016
Membranoproliferative glomerulonephritis represent a heterogeneous group of nephropathies. During the last five years, our understanding of membranoproliferative glomerulonephritis has greatly improved. Animal models and the study of complement genetics led to the dissection of the physiopathology of membranoproliferative glomerulonephritis, to the individualization of a new entity, C3 glomerulopathy, and to a new classification of these nephropathies. The study of large cohorts has also changed the clinical picture of membranoproliferative glomerulonephritis that has been long dominated by the severity of a single type of dense deposits disease. Finally, the rediscovery of complement through the study of the atypical haemolytic uremic syndrome and the availability in clinical practice of complement inhibitors have paved the way for new therapeutic approaches of membranoproliferative glomerulonephritis. © 2016 Association Société de néphrologie.