PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 879-885 ◽  
Author(s):  
Anastasia Guerriero ◽  
Peter B. Langmuir ◽  
Lisa M. Spain ◽  
Edward W. Scott
Keyword(s):  
Dendritic Cells ◽  
Interleukin 4 ◽  
Low Density ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Ets Family ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Mixed Lymphocyte Reactions

The ets-family transcription factor PU.1 is required for the proper development of both myeloid and lymphoid progenitors. We used PU.1-deficient animals to examine the role of PU.1 during dendritic cell development. PU.1−/−animals produce lymphoid-derived dendritic cells (DC): low-density class II major histocompatibility complex [MHC-II+] CD11c+ CD8+DEC-205+. But they lack myeloid-derived DC: low-density MHC-II+ CD11c+ CD8−DEC-205−. PU.1−/− embryos also lack progenitors capable of differentiating into myeloid DC in response to granulocyte-macrophage colony-stimulating factor plus interleukin-4. The appearance of lymphoid DC in developing PU.1−/−thymus was initially delayed, but this population recovered to wild type (WT) levels upon organ culture of isolated thymic lobes. PU.1−/−lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC.

Epstein-Barr virus inhibits the development of dendritic cells by promoting apoptosis of their monocyte precursors in the presence of granulocyte macrophage–colony-stimulating factor and interleukin-4

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3725-3734 ◽  
Author(s):  
LiQi Li ◽  
Daorong Liu ◽  
Lindsey Hutt-Fletcher ◽  
Andrew Morgan ◽  
Maria G. Masucci ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Epstein Barr Virus ◽  
Interleukin 4 ◽  
Viral Gene ◽  
Colony Stimulating Factor ◽  
Barr Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Epstein Barr ◽  
Macrophage Colony ◽  
Stimulating Factor

Epstein-Barr virus (EBV) is a tumorigenic human herpesvirus that persists for life in healthy immunocompetent carriers. The viral strategies that prevent its clearance and allow reactivation in the face of persistent immunity are not well understood. Here we demonstrate that EBV infection of monocytes inhibits their development into dendritic cells (DCs), leading to an abnormal cellular response to granulocyte macrophage–colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) and to apoptotic death. This proapoptotic activity was not affected by UV inactivation and was neutralized by EBV antibody-positive human sera, indicating that binding of the virus to monocytes is sufficient to alter their response to the cytokines. Experiments with the relevant blocking antibodies or with mutated EBV strains lacking either the EBV envelope glycoprotein gp42 or gp85 demonstrated that interaction of the trimolecular gp25–gp42–gp85 complex with the monocyte membrane is required for the effect. Our data provide the first evidence that EBV can prevent the development of DCs through a mechanism that appears to bypass the requirement for viral gene expression, and they suggest a new strategy for interference with the function of DCs during the initiation and maintenance of virus-specific immune responses.

scholarly journals Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites

1998 ◽  
Vol 188 (2) ◽  
pp. 373-386 ◽  
Author(s):  
Marie-Caroline Dieu ◽  
Béatrice Vanbervliet ◽  
Alain Vicari ◽  
Jean-Michel Bridon ◽  
Elisabeth Oldham ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Mrna Expression ◽  
Interleukin 4 ◽  
Traffic Pattern ◽  
Gm Csf ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34+ hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony–stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-α or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34+ HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3α, but also to MIP-1α and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-α, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3β. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3α and MIP-3β, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3β responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3β is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3α mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3β mRNA specifically in T cell–rich areas, suggests a role for MIP-3α/CCR6 in recruitment of immature DCs at site of injury and for MIP-3β/CCR7 in accumulation of antigen-loaded mature DCs in T cell–rich areas.

scholarly journals Endocarditis-Associated Oral Streptococci Promote Rapid Differentiation of Monocytes into Mature Dendritic Cells

2005 ◽  
Vol 73 (8) ◽  
pp. 5015-5021 ◽  
Author(s):  
Chin-Lo Hahn ◽  
Harvey A. Schenkein ◽  
John G. Tew
Keyword(s):  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Mononuclear Cells ◽  
Oral Bacteria ◽  
Interleukin 12 ◽  
Oral Streptococci ◽  
Peripheral Blood Mononuclear ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Mixed Lymphocyte Reactions

ABSTRACT Endocarditis is frequently attributable to oral streptococci, but mechanisms of pathogenesis are not well understood, although monocytes appear to be important. High titers of interleukin-12 (IL-12) are produced by peripheral blood mononuclear cells (PBMC) after engaging Streptococcus mutans, but monocytes in developing endocardial vegetations tend to disappear rather than become macrophages. These data prompted the hypothesis that streptococcus-infected monocytes differentiate into short-lived IL-12-producing dendritic cells (DCs) rather than macrophages. PBMC from healthy subjects were stimulated with six isolates of oral streptococci, three nonstreptococcal oral bacteria, or IL-4 plus granulocyte-macrophage colony-stimulating factor, and the appearance of cells with markers typical of mature DCs (CD83+, CD86+, CD11c+, and CD14−) was monitored. Supernatant fluids from the PBMC cultures were harvested and IL-12 p70 levels were determined. S. mutans-stimulated monocytes were analyzed for their ability to elicit allogeneic mixed-lymphocyte reactions. All streptococci examined, except one strain of Streptococcus oralis (35037), rapidly induced up-regulation of CD83 and CD86 and a loss of CD14 in the CD11c+ monocyte population within 20 h. Induction of IL-12 was CD14 dependent and correlated with streptococcal isolates that promoted the DC phenotype. Major histocompatibility complex (MHC) class II expression was up-regulated by S. mutans, and these cells were short-lived and elicited potent allogeneic mixed-lymphocyte reactions typical of DCs. In summary, monocytes stimulated with endocarditis-associated oral streptococci rapidly exhibited the DC phenotype and functions. These data suggest that the initiation of bacterial endocarditis by oral streptococci may involve monocyte-to-DC differentiation, and this may help explain the low levels of macrophages in the site.

scholarly journals CX3CR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1099 ◽  
Author(s):  
Salvatore Sutti ◽  
Stefania Bruzzì ◽  
Felix Heymann ◽  
Anke Liepelt ◽  
Oliver Krenkel ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Liver Injury ◽  
Experimental Models ◽  
Interleukin 4 ◽  
Hepatic Inflammation ◽  
Gm Csf ◽  
Ccl4 Administration ◽  
Macrophage Colony

Recent evidence suggests that hepatic dendritic cells (HDCs) contribute to the evolution of chronic liver diseases. However, the HDC subsets involved and the mechanisms driving these responses are still poorly understood. In this study, we have investigated the role of the fractalkine receptor CX3CR1 in modulating monocyte-derived dendritic cell (moDC) differentiation during liver inflammation. The phenotype of HDC and functional relevance of CX3CR1 was assessed in mice following necro-inflammatory liver injury induced by the hepatotoxic agent carbon tetrachloride (CCl4) and in steatohepatitis caused by a methionine/choline-deficient (MCD) diet. In both the experimental models, hepatic inflammation was associated with a massive expansion of CD11c+/MHCIIhigh/CD11b+ myeloid HDCs. These cells also expressed the monocyte markers Ly6C, chemokine (C-C Motif) receptor 2 (CCR2), F4/80 and CD88, along with CX3CR1, allowing their tentative identification as moDCs. Mice defective in CX3CR1 showed a reduction in liver-moDC recruitment following CCl4 poisoning in parallel with a defective maturation of monocytes into moDCs. The lack of CX3CR1 also affected moDC differentiation from bone marrow myeloid cells induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) in vitro. In wild-type mice, treatment with the CX3CR1 antagonist CX3-AT (150 µg, i.p.) 24 h after CCl4 administration reduced liver moDCS and significantly ameliorated hepatic injury and inflammation. Altogether, these results highlight the possible involvement of moDCs in promoting hepatic inflammation following liver injury and indicated a novel role of CX3CL1/CX3CR1 dyad in driving the differentiation of hepatic moDCs.

Sign in / Sign up

Export Citation Format

Share Document