Therefore, these two T3SEs induce caspase-3 activation in different cell types through very different means, with SipA inducing caspase-3 at the earliest time point in infection (i.e. epithelial cell entry) and SpvB later in infection upon SPI-2 expression in macrophages (Valle and Guiney, 2005; Browne et al., 2008; Srikanth et al., 2010). This evidence concerns the gene CASP3 and infection.