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.