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PLoS One. 2011 Feb 8;6(2):e16614. doi: 10.1371/journal.pone.0016614.

Role of cell-to-cell variability in activating a positive feedback antiviral response in human dendritic cells.

Author information

1
Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America.

Abstract

In the first few hours following Newcastle disease viral infection of human monocyte-derived dendritic cells, the induction of IFNB1 is extremely low and the secreted type I interferon response is below the limits of ELISA assay. However, many interferon-induced genes are activated at this time, for example DDX58 (RIGI), which in response to viral RNA induces IFNB1. We investigated whether the early induction of IFNBI in only a small percentage of infected cells leads to low level IFN secretion that then induces IFN-responsive genes in all cells. We developed an agent-based mathematical model to explore the IFNBI and DDX58 temporal dynamics. Simulations showed that a small number of early responder cells provide a mechanism for efficient and controlled activation of the DDX58-IFNBI positive feedback loop. The model predicted distributions of single cell responses that were confirmed by single cell mRNA measurements. The results suggest that large cell-to-cell variation plays an important role in the early innate immune response, and that the variability is essential for the efficient activation of the IFNB1 based feedback loop.

PMID:
21347441
PMCID:
PMC3035661
DOI:
10.1371/journal.pone.0016614
[Indexed for MEDLINE]
Free PMC Article

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