scholarly journals First Genomic Analysis of Dendritic Cells from Lung and Draining Lymph Nodes in Murine Asthma

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Thomas Tschernig ◽  
Christina Hartwig ◽  
Andreas Jeron ◽  
Quoc Thai Dinh ◽  
Marcus Gereke ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Lung Tissue ◽  
Cell Sorting ◽  
Allergic Inflammation ◽  
Genomic Analysis ◽  
T Cell Response ◽  
Transcriptional Analysis ◽  
Gene Arrays ◽  
Draining Lymph Nodes

Asthma is the consequence of allergic inflammation in the lung compartments and lung-draining lymph nodes. Dendritic cells initiate and promote T cell response and drive it to immunity or allergy. However, their modes of action during asthma are poorly understood. In this study, an allergic inflammation with ovalbumin was induced in 38 mice versus 42 control animals. After ovalbumin aerosol challenge, conventional dendritic cells (CD11c/MHCII/CD8) were isolated from the lungs and the draining lymph nodes by means of magnetic cell sorting followed by fluorescence-activated cell sorting. A comparative transcriptional analysis was performed using gene arrays. In general, many transcripts are up- and downregulated in the CD8−dendritic cells of the allergic inflamed lung tissue, whereas few genes are regulated in CD8+dendritic cells. The dendritic cells of the lymph nodes also showed minor transcriptional changes. The data support the relevance of the CD8−conventional dendritic cells but do not exclude distinct functions of the small population of CD8+dendritic cells, such as cross presentation of external antigen. So far, this is the first approach performing gene arrays in dendritic cells obtained from lung tissue and lung-draining lymph nodes of asthmatic-like mice.

scholarly journals Differential Recruitment of Dendritic Cells Subsets to Lymph Nodes Correlates with a Protective or Permissive T-Cell Response duringLeishmania(Viannia)BraziliensisorLeishmania(Leishmania)AmazonensisInfection

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
A. K. Carvalho ◽  
K. Carvalho ◽  
L. F. D. Passero ◽  
M. G. T. Sousa ◽  
V. L. R. da Matta ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
T Lymphocyte ◽  
Langerhans Cells ◽  
T Cell Response ◽  
Lymphocyte Response ◽  
Draining Lymph Nodes ◽  
Th1 Immune Response

Leishmania (L.) amazonensis(La) andL. (V.) braziliensis(Lb) are responsible for a large clinical and immunopathological spectrum in human disease; whileLamay be responsible for anergic disease,Lbinfection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by theseLeishmaniaspecies, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course ofLaandLbinfection in BALB/c mice. Our results demonstrated a high involvement of DCs inLainfection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely,Lbinfection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4+T-cells was observed inLbinfection. Interleukin- (IL-) 4- and IL-10-producing CD4+and CD8+T-cells were present in bothLaandLbinfection; however, interferon- (IFN-)γ-producing CD4+and CD8+T-cells were detected only inLbinfection. The results suggest that duringLbinfection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrastLainfection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.

scholarly journals Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity

2021 ◽  
Vol 118 (3) ◽  
pp. e2021364118
Author(s):  
Hannah L. Miller ◽  
Prabhakar Sairam Andhey ◽  
Melissa K. Swiecki ◽  
Bruce A. Rosa ◽  
Konstantin Zaitsev ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Diphtheria Toxin ◽  
Fluorescein Isothiocyanate ◽  
Skin Inflammation ◽  
Contact Hypersensitivity ◽  
Type I ◽  
Th2 Response ◽  
Draining Lymph Nodes

Plasmacytoid dendritic cells (pDCs) specialize in the production of type I IFN (IFN-I). pDCs can be depleted in vivo by injecting diphtheria toxin (DT) in a mouse in which pDCs express a diphtheria toxin receptor (DTR) transgene driven by the human CLEC4C promoter. This promoter is enriched for binding sites for TCF4, a transcription factor that promotes pDC differentiation and expression of pDC markers, including CLEC4C. Here, we found that injection of DT in CLEC4C-DTR+ mice markedly augmented Th2-dependent skin inflammation in a model of contact hypersensitivity (CHS) induced by the hapten fluorescein isothiocyanate. Unexpectedly, this biased Th2 response was independent of reduced IFN-I accompanying pDC depletion. In fact, DT treatment altered the representation of conventional dendritic cells (cDCs) in the skin-draining lymph nodes during the sensitization phase of CHS; there were fewer Th1-priming CD326+ CD103+ cDC1 and more Th2-priming CD11b+ cDC2. Single-cell RNA-sequencing of CLEC4C-DTR+ cDCs revealed that CD326+ DCs, like pDCs, expressed DTR and were depleted together with pDCs by DT treatment. Since CD326+ DCs did not express Tcf4, DTR expression might be driven by yet-undefined transcription factors activating the CLEC4C promoter. These results demonstrate that altered DC representation in the skin-draining lymph nodes during sensitization to allergens can cause Th2-driven CHS.

Case Studies Discussing the Pathology, Immunogenicity, and Proposed Mechanism of Toxicity of an Inhaled Anti-TGFβ Humanized Fab Antibody in Non-Human Primates and Mice

2020 ◽  
pp. 019262332096002
Author(s):  
Anthony Peter Hall ◽  
Annick Cauvin ◽  
Sherri Dudal ◽  
James Raymond ◽  
Petrina Rogerson ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Inflammatory Cell ◽  
Transforming Growth Factor ◽  
Systemic Exposure ◽  
Plasminogen Activator Inhibitor ◽  
Transforming Growth Factor Β ◽  
Lavage Fluid ◽  
T Cell Response ◽  
Plasminogen Activator Inhibitor 1 ◽  
Draining Lymph Nodes

Treatment of nonhuman primates and mice with a humanized antigen-binding fragment (Fab) antibody (UCBFab) inhibiting transforming growth factor β via daily inhalation for up to 13 weeks resulted in low systemic exposure but high local exposure in the lung. Target engagement was demonstrated by reduced levels of signal transducers, phosphoSMAD and plasminogen activator inhibitor-1 in the bronchoalveolar lavage fluid (BALF). Treatment was associated with a high frequency and titer of antidrug antibodies, indicating high local immunogenicity, and local pathology within the lung and draining lymph nodes. Microscopic changes were characterized by perivascular (PV) and peribronchiolar (PB) mononuclear inflammatory cell (MIC) infiltrates that were principally lymphocytic in nature and mixed inflammatory cell infiltrates and/or inflammation within the alveoli. Immunohistochemical investigation revealed a predominantly CD68-positive macrophage and CD3- and CD8>CD4-positive T-cell response in the alveoli, whereas within the airways, there was a variable mixture of CD3-positive T cells, CD20-positive B cells, and CD68-positive macrophages. Increased cellularity of the draining lymph nodes was also noted, indicating the presence of an immune response to the inhaled test article. Morphologic changes did not progress over time, and all changes partially recovered. Increased leukocytes (principally macrophages) in BALF cytology correlated with the changes seen by histopathology.

Plasmacytoid Dendritic Cells from Human Lung Cancer Draining Lymph Nodes Induce Tc1 Responses

2007 ◽  
Vol 36 (3) ◽  
pp. 360-367 ◽  
Author(s):  
Alexander Faith ◽  
Emma Peek ◽  
Joanne McDonald ◽  
Zoe Urry ◽  
David F. Richards ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Human Lung ◽  
Plasmacytoid Dendritic Cells ◽  
Human Lung Cancer ◽  
Draining Lymph Nodes

scholarly journals Expression of MIP-1α (CCL3) by a Recombinant Rabies Virus Enhances Its Immunogenicity by Inducing Innate Immunity and Recruiting Dendritic Cells and B Cells

2010 ◽  
Vol 84 (18) ◽  
pp. 9642-9648 ◽  
Author(s):  
Ling Zhao ◽  
Harufusa Toriumi ◽  
Hualei Wang ◽  
Yi Kuang ◽  
Xiaofeng Guo ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Dendritic Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
Rabies Virus ◽  
Mouse Brain ◽  
Peripheral Blood ◽  
Neutralizing Antibody ◽  
Antibody Titers ◽  
Draining Lymph Nodes

ABSTRACT Previously, we showed that overexpression of MIP-1α in mouse brain further decreased rabies virus (RABV) pathogenicity (L. Zhao, H. Toriumi, Y. Kuang, H. Chen, and Z. F. Fu, J. Virol., 83:11808-11818, 2009). In the present study, the immunogenicity of recombinant RABV expressing MIP-1α (rHEP-MIP1α) was determined. It was found that intramuscular immunization of BALB/c mice with rHEP-MIP1α resulted in a higher level of expression of MIP-1α at the site of inoculation, increased recruitment of dendritic cells (DCs) and mature B cells into the draining lymph nodes and the peripheral blood, and higher virus-neutralizing antibody titers than immunization with the parent rHEP and recombinant RABVs expressing RANTES (CCL5) or IP-10 (CXCL10). Our data thus demonstrate that expression of MIP-1α not only reduces viral pathogenicity but also enhances immunogenicity by recruiting DCs and B cells to the site of immunization, the lymph nodes, and the blood.

scholarly journals Simian Immunodeficiency Virus Rapidly Penetrates the Cervicovaginal Mucosa after Intravaginal Inoculation and Infects Intraepithelial Dendritic Cells

2000 ◽  
Vol 74 (13) ◽  
pp. 6087-6095 ◽  
Author(s):  
Jinjie Hu ◽  
Murray B. Gardner ◽  
Christopher J. Miller
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Genital Tract ◽  
Cell Suspensions ◽  
Specific Cell ◽  
Mucosal Surfaces ◽  
Immunodeficiency Virus ◽  
Primate Lentiviruses ◽  
Draining Lymph Nodes

ABSTRACT Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined formalin-fixed tissues and HLA-DR+-enriched cell suspensions to identify the cells containing SIV RNA in the genital tract and draining lymph nodes within the first 24 h of infection. Using SIV-specific fluorescent in situ hybridization combined with immunofluorescent antibody labeling of lineage-specific cell markers, numerous SIV RNA+ DC were documented in cell suspensions from the vaginal epithelium 18 h after vaginal inoculation. In addition, we determined the minimum time that the SIV inoculum must remain in contact with the genital mucosa for the virus to move from the vaginal lumen into the mucosa. We now show that SIV enters the vaginal mucosa within 60 min of intravaginal exposure, infecting primarily intraepithelial DC and that SIV-infected cells are located in draining lymph nodes within 18 h of intravaginal SIV exposure. The speed with which primate lentiviruses penetrate mucosal surfaces, infect DC, and disseminate to draining lymph nodes poses a serious challenge to HIV vaccine development.

scholarly journals Melanoma cell lysate induces CCR7 expression andin vivomigration to draining lymph nodes of therapeutic human dendritic cells

Immunology ◽  
2014 ◽  
Vol 142 (3) ◽  
pp. 396-405 ◽  
Author(s):  
Fermín E. González ◽  
Carolina Ortiz ◽  
Montserrat Reyes ◽  
Nicolás Dutzan ◽  
Vyomesh Patel ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Melanoma Cell ◽  
Ccr7 Expression ◽  
Cell Lysate ◽  
Human Dendritic Cells ◽  
Draining Lymph Nodes

How many dendritic cells are required to initiate a T-cell response?

Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 3945-3948 ◽  
Author(s):  
Susanna Celli ◽  
Mark Day ◽  
Andreas J. Müller ◽  
Carmen Molina-Paris ◽  
Grant Lythe ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
T Cell Activation ◽  
Cell Response ◽  
Rational Design ◽  
Cell Activation ◽  
T Cell Response ◽  
Cell Responses ◽  
Precursor Frequency

Abstract T-cell activation in lymph nodes relies on encounters with antigen (Ag)–bearing dendritic cells (DCs) but the number of DCs required to initiate an immune response is unknown. Here we have used a combination of flow cytometry, 2-photon imaging, and computational modeling to quantify the probability of T cell–DC encounters. We calculated that the chance for a T cell residing 24 hours in a murine popliteal lymph nodes to interact with a DC was 8%, 58%, and 99% in the presence of 10, 100, and 1000 Ag-bearing DCs, respectively. Our results reveal the existence of a threshold in DC numbers below which T-cell responses fail to be elicited for probabilistic reasons. In mice and probably humans, we estimate that a minimum of 85 DCs are required to initiate a T-cell response when starting from precursor frequency of 10−6. Our results have implications for the rational design of DC-based vaccines.

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