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Assessing the Development of Murine Plasmacytoid Dendritic Cells in Peyer's Patches Using Adoptive Transfer of Hematopoietic Progenitors
Published on: March 17, 2014
Neonatal plasmacytoid dendritic cells (pDCs) display subset variation but can elicit potent anti-viral innate
Xiaoming Zhang1, Alice Lepelley, Elie Azria
1Régulation Immunitaire et Vaccinologie, Institut Pasteur, Paris, France.
Insights
Neonatal immune cells called plasmacytoid dendritic cells (pDCs) show distinct characteristics but maintain robust antiviral responses. Despite variations in their subsets, these pDCs effectively combat viral infections in newborns.
Area of Science:
- Immunology
- Neonatal Immunity
- Infectious Diseases
Background:
- Neonates exhibit increased susceptibility to infections, potentially due to impaired antiviral immune responses.
- Plasmacytoid dendritic cells (pDCs) play a crucial role in antiviral immunity through cytokine production.
Purpose of the Study:
- To investigate the functional and phenotypic characteristics of neonatal pDCs compared to adult pDCs.
- To determine the impact of neonatal pDC variations on antiviral responses.
Main Methods:
- Isolation and analysis of peripheral blood mononuclear cells (PBMCs) from cord blood and adult blood.
- Flow cytometry to assess pDC subsets (CD2+, CD5+).
- Stimulation assays with various viruses (IAV, HIV, HSV) and CpG-oligonucleotides (CpGA).
- Measurement of cytokine production (IFN-α, TNF-α, IL-12p40) and pDC survival.
Main Results:
- Cord blood pDCs demonstrated innate antiviral responses, producing IFN-α, TNF-α, and chemokines upon viral stimulation.
- Neonatal pDCs showed an expanded CD2+pDC compartment compared to adults, without compromising IFN-α production.
- A decrease in the CD5+ subpopulation, responsible for IL-12p40 production, was observed in neonatal pDCs.
Conclusions:
- Neonatal pDCs exhibit unique phenotypic and subset compositions, including an increased CD2+ compartment and reduced CD5+ subset.
- Despite these differences, neonatal pDCs maintain effective antiviral responses, particularly IFN-α production.
- The observed variations in neonatal pDC subsets do not appear to significantly impair their crucial role in combating viral infections.
Abstract:
Neonates are highly susceptible to infectious diseases and defective antiviral pDC immune responses have been proposed to contribute to this phenomenon. Isolated cord blood pDCs innately responded to a variety of TLR7 and TLR9 dependent viruses, including influenza A virus (IAV), human immunodeficiency virus (HIV) or herpes-simplex virus (HSV) by efficiently producing IFN-α, TNF-α as well as chemokines. Interestingly, following activation by CpGA, but not viruses, cord pDCs tend to survive less efficiently. We found that a hallmark of pDCs in neonates is an extended CD2+pDCs compartment compared to adult pDCs without affecting the antiviral IFN-α response. Within CD2+pDCs, we identified a subpopulation expressing CD5 and responsible for IL-12p40 production, however this population is significantly decreased in cord blood compared to adult blood. Therefore, neonatal pDCs clearly display variation in phenotype and subset composition, but without major consequences for their antiviral responses.
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