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Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Effects of feline immunodeficiency virus on feline monocyte-derived dendritic cells infected by spinoculation
G Freer1, D Matteucci1, P Mazzetti1
1Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, Via del Brennero 2, I-56127 Pisa, Italy.
Insights
Feline immunodeficiency virus (FIV) infects feline dendritic cells (DCs), which can then spread the virus to T cells. Despite infection, these feline DCs maintain their function and can still activate immune responses.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Type 1 human immunodeficiency virus (HIV) infects dendritic cells (DCs), which can prime and infect T cells.
- Feline immunodeficiency virus (FIV) causes Feline AIDS, a model for human HIV, but FIV-DC interactions are poorly understood.
Purpose of the Study:
- To investigate the interaction between feline monocyte-derived dendritic cells (MDDCs) and FIV.
- To determine if FIV infects feline MDDCs and how this infection affects DC function and T cell activation.
Main Methods:
- Feline MDDCs were infected with FIV strains Petaluma (FIV-Pet) and M2 via spinoculation.
- Viral production was monitored by quantifying viral content in supernatants, intracellular p25 staining, and observing cytopathic effects.
- FIV receptor expression (CD134, CXCR4) on MDDCs was analyzed.
Main Results:
- FIV-Pet was produced by both immature and lipopolysaccharide-matured feline MDDCs, as well as by activated T cells.
- Feline MDDCs exhibited syncytium formation at later stages post-infection.
- MDDCs expressed CXCR4 but not CD134, indicating permissiveness to FIV-Pet.
- FIV infection did not impair MDDC maturation or function.
- Infected MDDCs efficiently infected peripheral blood mononuclear cells (PBMCs) in trans.
Conclusions:
- Feline MDDCs are permissive to FIV infection.
- FIV infection does not significantly alter feline MDDC functionality.
- Infected feline MDDCs can serve as a source of FIV for T cells, contributing to viral spread.
Abstract:
During type 1 human immunodeficiency virus infection, not only can dendritic cells (DCs) prime T cells against the virus, but they can also infect them in trans. Feline AIDS is caused by feline immunodeficiency virus (FIV) and is considered a model for the human illness because the two diseases have many features in common. Little is known about the interaction of feline DCs with FIV; therefore, this study attempts to tackle such an issue. Infection of feline monocyte-derived DCs (MDDCs) was attempted by spinoculation with FIV strains Petaluma (FIV-Pet) and M2. FIV-Pet was released rapidly in the supernatants of both infected MDDCs and activated T cells after spinoculation. It is shown that FIV-Pet was produced by MDDCs by monitoring viral content in the supernatants of infected MDDCs, by intracellular staining for p25 and by showing its cytopathic effect. Although activated T cells were better substrates for FIV replication, leading to prolonged viral shedding, both immature MDDCs and MDDCs matured with lipopolysaccharide supported virus production, mostly during the first 2 days after infection. At later times, FIV induced syncytium formation by MDDCs. Concerning the FIV receptors, MDDCs were shown to be CD134-negative and CXCR4-positive, a phenotype compatible with permissiveness to FIV-Pet. These results also suggest that maturation is not hampered by FIV infection and that virus exposure itself does not induce MDDC maturation. It is also shown that infected MDDCs can infect activated PBMCs efficiently in trans. It is concluded that MDDCs can be infected by FIV, although infection does not appear to influence their functionality.
