Programmed cell death (PCD) assures the removal of infected cells and is therefore crucial for the host defence against intracellular pathogens. It has become apparent that PCD pathways (pyroptosis, apoptosis and necroptosis) are tightly interconnected and regulated by a remarkable level of redundancy. The generation of mice lacking caspases-1/-11/-12 and -8 allowed us to not only study the individual roles of different caspases in PCD processes under conditions where other key caspases required for the host response are absent but to define new mechanisms of apoptosis induction during Salmonella infection. To investigate the importance of caspase-2 for apoptosis during Salmonella Typhimurium infection, we compared caspase-2 deficient and caspases-1/-11/-12/-8/-2/RIPK3 deficient mice to prevent compensatory effects of other caspases. Our findings revealed that the absence of caspase-2 caused no major impairments of Salmonella control and therefore argue against a significant role for caspase-2 in apoptosis induction. Because Salmonella infections stimulate a robust IFN-γ-producing CD4 T cells response, we next analysed if apoptosis of infected cells is induced via IFN-γ-driven mechanisms. Our findings that IFN-γ and interferon regulatory factor 1 (IRF1) deficient mice have comparably elevated bacterial titres after Salmonella infection suggests that IRF1 is the main transcription factor downstream of IFN-γ signalling. In line with this, the impaired Salmonella control in mice lacking the IRF1-regulated factors TNF-α, Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) indicate their importance for apoptosis induction. Additionally, T cell depletion in pyroptosis deficient mice, which rely on apoptotic PCD to control intracellular pathogens, resulted in significantly elevated bacterial titres highlighting the role of CD4 T cells in apoptosis induction. Based on our findings we hypothesize that IFN-γ production of T cells activated by cytokines released during pyroptotic cell death can sensitize macrophages via IRF1-driven up-regulation of TNF receptor superfamily members to CD4 T cell-induced apoptosis.