New research co-authored by Marek Kimmel, professor of statistics, demonstrates a “switch-like” cell response to virus particle, or virion, penetration.
“What we are dealing with is innate immunity as opposed to adaptive immunity,” Kimmel said. “This is the most primitive, first-line immune response.”
The innate immune-system processes pathogen-induced signals into cell-fate decisions to restrict the spread of pathogens. How information is turned into a decision was previously unknown. This new research provides a mathematical, model-based explanation.
With adaptive immunity, as seen in bacteria, the cell response is pulse-like. Exposure to the bacterial membrane triggers the cell, causing the cell to produce a wave of small proteins called cytokines. The cytokines stimulate further, adaptive stages of immunity that eliminate the pathogens or prevent their growth.
Innate immunity, in response to a virus, causes the cell to produce particles that warn other cells of the virus’s presence.
As the virion attempts to enter a cell, it binds to a receptor. The receptor then sends a signal that determines the fate of the cell.
“With the so-called switch-like response,” Kimmel said, “the cell will first wait a bit and produce a wave of information, and then it commits apoptosis [self-termination] to kill the virions already inside it.”
That wave of information sent by the cell tells its immediate neighbors how quickly they should commit apoptosis, and sends a message to other nearby cells to be on standby.
“Each place where a virion is penetrating is a center of the cell response,” Kimmel said. “Once the threat is over, the response subsides.”
The researchers built a model at the level of a single-cell and proposed how the switch-like process works in cooperating cells.
“We took known facts about the chemical reactions that guide the cell response, and then performed additional experiments to be able to estimate parameters of these reaction rates.”
The group took its findings and built a to-scale model, to study how their predictions compared with experimental results.
Kimmel said it is significant that their technique, known to work in smaller models, works at large scales.
A paper on the work, titled “Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways,” was published in Nature Communications in February.
Co-authors include Sławomir Błoński, Karolina Tudelska, Joanna Jaruszewicz-Błońska, Marek Kochańczyk, Wiktor Prus, Zbigniew Korwek, and Maciej Czerkies, all of the Institute of Fundamental Technological Research of the Polish Academy of Sciences, Allan R. Brasier of the University of Texas Medical Branch, and Tomasz Lipniacki of the Polish Academy of Sciences.
The paper is a refinement of a previous modeling study, with partly overlapping authorship, published in PLOS ONE in April 2014. The paper, titled, “Dynamic cross talk model of the epithelial innate immune response to double-stranded RNA stimulation: coordinated dynamics emerging from cell-level noise,” was authored by Roberto Bertolusso of Rice University, Bing Tian, Yingxin Zhao, and Leonardo Vergara of the University of Texas Medical Branch, Aqeeb Sabree of Rice University, Marta Iwanaszko of Silesia University of Technology, Tomasz Lipniacki of the Polish Academy of Sciences, Allan R. Brasier of the University of Texas Medical Branch, and Kimmel.