Unraveling the dose-response puzzle of L. monocytogenes: A mechanistic approach

Food-borne disease outbreaks caused by Listeria monocytogenes continue to impose heavy burdens on public health in North America and globally. To explore the threat L. monocytogenes presents to the elderly, pregnant woman and immuno-compromised individuals, many studies have focused on in-host infection mechanisms and risk evaluation in terms of dose-response outcomes. However, the connection of these two foci has received little attention, leaving risk prediction with an insufficient mechanistic basis. Consequently, there is a critical need to quantifiably link in-host infection pathways with the dose-response paradigm. To better understand these relationships, we propose a new mathematical model to describe the gastro-intestinal pathway of L. monocytogenes within the host. The model dynamics are shown to be sensitive to inoculation doses and exhibit bi-stability phenomena. Applying the model to guinea pigs, we show how it provides useful tools to identify key parameters and to inform critical values of these parameters that are pivotal in risk evaluation. Our preliminary analysis shows that the effect of gastro-environmental stress, the role of commensal microbiota and immune cells are critical for successful infection of L. monocytogenes and for dictating the shape of the dose-response curves.