Details

Autor(en) / Beteiligte

• Jonas, Daniel
• Kirby, Michael
• Schenkel, Alan R.
• Dangelmayr, Gerhard

Titel

Modeling of adaptive immunity uncovers disease tolerance mechanisms

Ist Teil von

• Journal of theoretical biology, 2023-07, Vol.568, p.111498-111498, Article 111498

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• When an organism is challenged with a pathogen a cascade of events unfolds. The innate immune system rapidly mounts a preliminary nonspecific defense, while the acquired immune system slowly develops microbe-killing specialists. These responses cause inflammation, and along with the pathogen cause direct and indirect tissue damage, which anti-inflammatory mediators seek to temper. This interplay of systems is credited for maintaining homeostasis but may produce unexpected results such as disease tolerance. Tolerance is characterized by the persistence of pathogen and damage mitigation, where the relevant mechanisms are poorly understood. In this work we develop an ordinary differential equations model of the immune response to infection in order to identify key components in tolerance. Bifurcation analysis uncovers health, immune- and pathogen-mediated death clinical outcomes dependent on pathogen growth rate. We demonstrate that decreasing the inflammatory response to damage and increasing the strength of the immune system gives rise to a region in which limit cycles, or periodic solutions, are the only biological trajectories. We then describe areas of parameter space corresponding to disease tolerance by varying immune cell decay, pathogen removal, and lymphocyte proliferation rates. •A novel immune system model produces health, death, and disease tolerance outcomes.•Response to tissue damage and strength of acquired immunity contribute to tolerance.•The frequency of pathogen surges within a tolerant host increases with virulence.