Immunofluorescence image showing cells that have undergone a form of regulated cell death called pyroptosis. Image credit: Zachary Billman (CC BY 4.0).
Although alive and healthy cells are essential for survival, in certain circumstances – such as when a cell becomes infected – it is beneficial for cells to deliberately die through a process known as regulated cell death. There are several types of regulated cell death, each with distinct pathways and mechanisms. However, if the initial pathway is blocked, cells can use an alternative one, suggesting that they can compensate for one other.
Two forms of regulated cell death – named pyroptosis and apoptosis – can be used by infected cells to limit the spread of pathogens. However, it was not clear if these two forms or additional ‘back-up’ apoptosis pathways – which are induced when pyroptosis fails – are equally efficient at clearing infections and how they might vary in different cell types.
To address this, Abele et al. investigated cell death in live mice infected with the bacterium Salmonella. Different organs in which the bacterium infects distinct cell types were examined. Experiments showed that pyroptosis could eliminate bacteria from both intestinal cells as well as immune cells found throughout the body, called macrophages. In contrast, apoptosis was only able to clear infection from intestinal cells.
The findings can be explained by prior studies showing both apoptosis and pyroptosis lead to the same outcome in intestinal cells – dead cells are expelled from the body through a process called extrusion to maintain the barrier function of the intestine. However, in macrophages, the different pathways lead to different outcomes, indicating they are not entirely interchangeable.
Overall, the findings of Abele et al. underscore the complexity of cellular responses to infection and the nuanced roles of different cell death pathways. This provides further evidence that cells might have specific tasks they need to complete before death in order to effectively clear an infection. These tasks may differ depending on cell type and the form of regulated cell death, and may not be equally efficient at clearing an infection.
