Role of Cell-to-cell Variability in Activating a Positive Feedback Antiviral Response in Human Dendritic Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Feb 25

PMID 21347441

Citations 22

Authors

Jianzhong Hu

German Nudelman

Yishai Shimoni

Madhu Kumar

Yaomei Ding

Carolina Lopez

Fernand Hayot

James G Wetmur

Stuart C Sealfon

Affiliations

Soon will be listed here.

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.

Citing Articles

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Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells.

Wimmers F, Subedi N, van Buuringen N, Heister D, Vivie J, Beeren-Reinieren I Nat Commun. 2018; 9(1):3317.

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