A Rose by any Other Name: Towards a quantitative theory of memory in neuroimmune interactions

Abstract

Humanity has known about - and been fascinated by - the connection between mind and body since time immemorial, yet we have only been able to begin to quantitatively explore their interactions in recent years. Even so, the field of neuroimmunology is categorically in its infancy. Despite myriad and diverse experimental reports, no coherent theoretical approach to the neuroimmune system has been even attempted, which makes it difficult to make sense of the emerging body of empirical findings. Here, we take the first steps towards this goal by introducing a mathematical framework that describes the triggering and control of neurological memories (engrams) of immune challenges. Using peanut allergies as a model system, we show how a simple differential equation model of coupled immune-engram responses can explain a number of key observations regarding putative neurological control of focal inflammatory responses and failures thereof. Simulations of our model identify four areas of the parameter regime corresponding to distinct consequences of fake immune stimulation: a) resolution b) finite oscillations of inflammation, followed by resolution c) sustained, self-amplifying oscillations (cytokine storm-like phenomena) and d) resolution followed by the permanent establishment of a chronic higher-baseline inflammatory state. Importantly, we then show how our model recapitulates the key qualitative features of a recent experimental description of immune engram encoding and re-activation (respectively, suppression) in a mouse model of colitis. We conclude with remarks around clinical implications as well as directions for future work in theoretical neuroimmunology. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/605114v3_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@89ea55org.highwire.dtl.DTLVardef@778323org.highwire.dtl.DTLVardef@428edforg.highwire.dtl.DTLVardef@1b1deea_HPS_FORMAT_FIGEXP M_FIG C_FIG