Epithelial stratification shapes infection dynamics.

Carmen Lía Murall,Michel Segondy,Ingeborg Zehbe,Robert Jackson,Nathalie Boulle,Samuel Alizon,Marc D Ryser

doi:10.1371/journal.pcbi.1006646

Abstract

Infections of stratified epithelia contribute to a large group of common diseases, such as dermatological conditions and sexually transmitted diseases. To investigate how epithelial structure affects infection dynamics, we develop a general ecology-inspired model for stratified epithelia. Our model allows us to simulate infections, explore new hypotheses and estimate parameters that are difficult to measure with tissue cell cultures. We focus on two contrasting pathogens: Chlamydia trachomatis and Human papillomaviruses (HPV). Using cervicovaginal parameter estimates, we find that key infection symptoms can be explained by differential interactions with the layers, while clearance and pathogen burden appear to be bottom-up processes. Cell protective responses to infections (e.g. mucus trapping) generally lowered pathogen load but there were specific effects based on infection strategies. Our modeling approach opens new perspectives for 3D tissue culture experimental systems of infections and, more generally, for developing and testing hypotheses related to infections of stratified epithelia.

Highlights

Stratified epithelia cover most of the human body’s exterior and line the inner cavities, such as the mouth and vagina
Many epithelia are stratified in layers of cells and their infection can result in many pathologies, from rashes to cancer
It is important to understand to what extent the epithelial structure determines infection dynamics and outcomes

Summary

Introduction

Stratified epithelia cover most of the human body’s exterior and line the inner cavities, such as the mouth and vagina. Localized (non-systemic) infections of these epithelia can cause a wide range of conditions that collectively represent a major burden on global public health systems. Infections (viral, fungal, bacterial, etc.) are either the etiological agents or are secondary opportunistic infections (e.g. scabies, eczema) of many skin conditions and play a major role in their burden and outcomes. While stratified epithelia are often the first line of defense against infections [2], their cells are the primary target for many viruses or bacteria. This is why understanding epithelial life-cycles, signaling, and dynamics is an active line of research [3]

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Conclusion