The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

Vollstedt, Sabine; O’Keeffe, Meredith; Ryf, Beat; Glanzmann, Bettina; Hochrein, Hubertus; Suter, Mark

doi:10.1002/eji.200535759

Cited by 10 publications

(22 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An identical delay in viral clearance from the cornea was observed when DCs were persistently depleted by DT treatment at −2, +1, and +3 dpi, suggesting a specific role in viral clearance for the cornea resident DC population or those infiltrating the cornea during the first 24 hours after infection. Although plasmacytoid DCs (pDC) are a major source of type I interferon in HSV-1 infected mice (33,34), pDCs are not present in the normal cornea, and are not depleted by DT treatment of CD11c-DTR mice(35). Therefore, we proposed that the delay in HSV-1 clearance following DC depletion did not reflect direct viral clearance by DCs, but rather DC regulation of another cell type that is the proximal mediator of viral clearance from the cornea.…”

Section: Discussionmentioning

confidence: 99%

Early Responding Dendritic Cells Direct the Local NK Response To Control Herpes Simplex Virus 1 Infection within the Cornea

Frank

Buela

Maker

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Dendritic cells (DCs) regulate both innate and adaptive immune responses. Here we exploit the unique avascularity of the cornea to examine a role for local or very early infiltrating DCs in regulating the migration of blood-derived innate immune cells towards herpes simplex virus type 1 (HSV-1) lesions. A single systemic diphtheria toxin (DT) treatment 2 days before HSV-1 corneal infection transiently depleted CD11c+DCs from both the cornea and lymphoid organs of CD11c-DTR bone marrow chimeric mice for up to 24 hours after infection. Transient DC depletion significantly delayedHSV-1 clearance from the corneathrough 6 days post infection(dpi). No further compromise of viral clearance was observed when DCs were continuously depleted throughout the first week of infection. DC depletion did not influenceextravasation of NK cells, inflammatory monocytes, orneutrophils into the peripheral cornea,but did significantly reduce migration of NK cells and inflammatory monocytes, but not neutrophils towards the HSV-1 lesion in the central cornea. Depletion of NK cells resulted in similar loss of viral control to transient DC ablation. Our findings demonstrate resident corneal DC and/or those that infiltrate the cornea during the first 24 hours after HSV-1 infection contribute to the migration of NK cells and inflammatory monocytes into the central cornea, and are consistent with a role for NK cells and possibly inflammatory monocytes, but not PMN in the clearing HSV-1 from the infected cornea.

show abstract

Section: Discussionmentioning

confidence: 99%

Early Responding Dendritic Cells Direct the Local NK Response To Control Herpes Simplex Virus 1 Infection within the Cornea

Frank

Buela

Maker

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Some of these same conditions have also been reported to enhance circulating M-CSF levels. For example, the serum of patients with Langerhans cell histiocytosis displays increased FL and M-CSF, 30 viral infections and IFN-␣, both shown to increase circulating FL, also increase M-CSF, [31][32][33][34] the serum of patients with systemic lupus erythematosus (SLE) has increased FL 35 , and animal models of SLE report elevated M-CSF levels. 36 Within these settings, the simultaneous elevation of FL and M-CSF, with M-CSF previously not suggested as capable of enhancing DC subsets, potentiates a cooperative role for these growth factors in DC development.…”

Section: Discussionmentioning

confidence: 99%

M-CSF: a novel plasmacytoid and conventional dendritic cell poietin

Fancke

Suter

Hochrein

et al. 2008

Blood

Self Cite

View full text Add to dashboard Cite

The critical importance of plasmacytoid dendritic cells (pDCs) in viral infection, autoimmunity, and tolerance has focused major attention on these cells that are rare in blood and immune organs of humans and mice. The recent development of an Flt-3 ligand (FL) culture system of bone marrow cells has led to the simple generation of large numbers of pDCs that resemble their in vivo steady-state counterparts. The FL system has allowed unforeseen insight into the biology of pDCs, and it is assumed that FL is the crucial growth factor for these cells. Surprisingly we have found that a cell type with high capacity for interferon-␣ (IFN-␣)

show abstract

“…This defect is detected both at the protein and mRNA levels. Interestingly, long-term resistance to HSV-1 could be induced in neonatal mice following IFN-a treatment at birth, highlighting the decisive role of IFN-a and pDC for viral resistance in early life [19]. The fact that TLR7-dependent type I IFN synthesis is impaired in cord blood pDC suggests that cord blood pDC responses to singlestranded RNA viruses would be also compromised.…”

Section: Discussionmentioning

confidence: 99%

Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

et al. 2008

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDC) are specialized in massive production of type I interferons (IFN) upon viral infections. Activation of IFN regulatory factor (IRF)-7 is critically required for the synthesis of type I IFN in pDC. IRF-7 is highly expressed by resting pDC and translocates into the nucleus to initiate type I IFN transcription. In a previous work, we observed an impaired IFN-a production in enriched cord blood pDC following a TLR9 stimulation using CpG oligonucleotides. Herein, we show that highly purified pDC from cord blood exhibit a profound defect in their capacity to produce IFN-a/b in response to TLR9 as well as to TLR7 ligation or human CMV or HSV-1 exposure. Microarray experiments indicate that expression of the majority of type I IFN subtypes induced by a TLR7 agonist is reduced in cord blood pDC. We next demonstrated a reduced nuclear translocation of IRF-7 in cord blood pDC following CpG and HSV stimulation as compared to adult pDC. We conclude that impaired IRF-7 translocation in cord blood pDC is associated with defective expression of type I IFN genes. Our data provide a molecular understanding for the decreased ability of cord blood pDC to produce type I IFN upon viral stimulation.

show abstract

The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

Cited by 10 publications

References 37 publications

Early Responding Dendritic Cells Direct the Local NK Response To Control Herpes Simplex Virus 1 Infection within the Cornea

Early Responding Dendritic Cells Direct the Local NK Response To Control Herpes Simplex Virus 1 Infection within the Cornea

M-CSF: a novel plasmacytoid and conventional dendritic cell poietin

Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

Contact Info

Product

Resources

About