Pathogenic bacteria promote infection largely through proteins and protein complexes they secrete and deliver into human cells or which alter cell signaling via binding to cell surface molecules. Bacterial molecules that interact with cells trigger human cell-type specific responses that are designed to restrict the infection. Our focus is to understand (1) the function of these secreted and delivered bacterial proteins, particularly during infection by Shigella and other gram-negative bacterial pathogens, (2) the mechanisms of cellular responses, particularly for epithelial cells, macrophages, and endothelial cells, and (3) how host organismic responses go awry, particularly during bacterial sepsis.