Here, we use HIOs derived from the H9 human embryonic stem cell line to define the host transcriptional response to infection by the commonly used laboratory strain S. Typhimurium SL1344 compared to isogenic mutants lacking functional SPI-1 or SPI-2 type 3 secretion systems (T3SS), major virulence determinants of S. Typhimurium that inject effector proteins into the host for cellular invasion and remodeling of host processes (8, 9). Here, SPI1 is linked to infection.