Fig. 4.

Host response to Typhi infection: barrier function and antigen trafficking.

(A) Differentially expressed genes cluster in cytoskeletal modulation pathways. Genes with an unidentified relationship to the pathway are shown in black; genes involved in pathway inhibition are shown in blue.

(B, H) Reorganization of the cytoskeletal is observed upon STY association with intestinal biopsies and organoid-derived epithelial monolayers (H). Large scale bars are 2 μm, small scale bars are 500 nm.

(C) Cellular protrusions are actin-dense as observed by immunostaining (C, circled).

(D–F) No changes in paracellular permeability (D, E) are observed at early time points during infection supporting the fact that STY directly infected enterocytes of the intestinal epithelium, and that biopsy invasion is not accompanied by cell death (F).

(G) Inhibition of the cytoskeleton using the actin inhibitor cytochalasin D or microtubule inhibitor nocodazole block STY entry into organoid-derived epithelial monolayers.

(H) STY bacteria interact with the epithelium by promoting cytoskeletal rearrangement and internalization into vesicles like those observed in the infected biopsies. Invading and intracellular STY are observed by TEM, green arrows. Cytoskeletal rearrangements are denoted by * and enterocytes are labeled with “E.” Large scale bars are 2 μm, small scale bars are 500 nm.