Chronic Inflammation in the Epidermis: A Mathematical Model

Abstract

The epidermal tissue is the outmost component of the skin that plays an important role as a first barrier system in preventing the invasion of various environmental agents, such as bacteria. Recent studies have identified the importance of microbial competition between harmful and beneficial bacteria and the diversity of the skin surface on our health. We develop mathematical models (M1 and M2 models) for the inflammation process using ordinary differential equations and delay differential equations. In this paper, we study microbial community dynamics via transcription factors, protease and extracellular cytokines. We investigate possible mechanisms to induce community composition shift and analyze the vigorous competition dynamics between harmful and beneficial bacteria through immune activities. We found that the activation of proteases from the transcription factor within a cell plays a significant role in the regulation of bacterial persistence in the M1 model. The competition model (M2) predicts that different cytokine clearance levels may lead to a harmful bacteria persisting system, a bad bacteria-free state and the co-existence of harmful and good bacterial populations in Type I dynamics, while a bi-stable system without co-existence is illustrated in the Type II dynamics. This illustrates a possible phenotypic switch among harmful and good bacterial populations in a microenvironment. We also found that large time delays in the activation of immune responses on the dynamics of those bacterial populations lead to the onset of oscillations in harmful bacteria and immune activities. The mathematical model suggests possible annihilation of time-delay-driven oscillations by therapeutic drugs.

Keywords

• epidermis
• mathematical model
• bacterial inflammation
• bacterial competition