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

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.

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Plasmacytoid dendritic cells regulate host immune response to Citrobacter rodentium induced colitis in colon‐draining lymph nodes

European Journal of Immunology ◽

10.1002/eji.202048714 ◽

2020 ◽

Author(s):

Sakari Pöysti ◽

Satu Silojärvi ◽

Raine Toivonen ◽

Arno Hänninen

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Lymph Nodes ◽

Host Immune Response ◽

Plasmacytoid Dendritic Cells ◽

Citrobacter Rodentium ◽

Draining Lymph Nodes

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

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/rcmb.2006-0284oc ◽

2007 ◽

Vol 36 (3) ◽

pp. 360-367 ◽

Cited By ~ 21

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

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1107 In Vitro Generated Human Dendritic Cells Exposed to a Potent Maturation Melanoma Cell Lines Lysate Show a Tolerogenic-like Phenotype and Functionality When Exposed to Dexamethasone Prior to the Maturation Stimuli

European Journal of Cancer ◽

10.1016/s0959-8049(12)71710-0 ◽

2012 ◽

Vol 48 ◽

pp. S267

Author(s):

C. Falcon-Beas ◽

F. Tempio ◽

B. Pesce ◽

J. Aguillon ◽

C. Pereda ◽

...

Keyword(s):

Dendritic Cells ◽

Cell Lines ◽

Melanoma Cell ◽

Human Dendritic Cells ◽

Melanoma Cell Lines

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

Journal of Virology ◽

10.1128/jvi.00326-10 ◽

2010 ◽

Vol 84 (18) ◽

pp. 9642-9648 ◽

Cited By ~ 49

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.

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

Journal of Virology ◽

10.1128/jvi.74.13.6087-6095.2000 ◽

2000 ◽

Vol 74 (13) ◽

pp. 6087-6095 ◽

Cited By ~ 386

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.

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