Sequential invasion of epithelial and immune cells in Shigellosis

Abstract

Shigella flexneri, the agent of shigellosis, invades the colonic mucosa, which leads to mucosal erosion, blood and immune cell infiltration, culminating in the hallmark of the disease, bloody diarrhea. Here, we conducted a microscopy-based analysis of time-resolved infection experiments in the infant rabbit model of shigellosis. We observed two stages of infection in the colonic tissue. During the early stage of infection, bacteria invaded and spread in epithelial cells, which correlated with mucosal erosion and blood infiltration. During the late stage of infection, the bacteria transitioned from their primary niche, the epithelial compartment, to their secondary niche, the lamina propria. Transcriptomic analysis of the late stage of infection assigned identities to various epithelial, immune, and stromal cells. The vast majority of the bacteria were associated with neutrophils or macrophages during the late stage of infection. We provide a discussion of how this model compares and contrasts with previous models of shigellosis.