Cell Death and Infection: Implications for Host and Microbe

Cell death is a part of life. Every day, billions of cells undergo programmed cell death within the human body as part of normal tissue turnover and homeostasis. The factors that initiate programmed cell death, the resulting signalling pathways that occur within the dying cell, the means to dispose of the dying cell, and the response of the neighbouring tissue to the dying cell are all highly evolutionarily conserved and tightly regulated processes. Decades of outstanding research have identified critical components of programmed cell death initiation, corpse clearance, and tissue response, particularly in the context of homeostatic cell death or sterile injury-induced cell death; however, multiple tissues are not sterile under homeostasis. In particular, the intestinal and respiratory tracts are 'external environment-facing' tissues that are in constant contact with commensal microorganisms and are also frequently exposed to invading pathogenic microbes. Indeed, many pathogenic microbes are capable of inducing or inhibiting various forms of cell death during infection, and some go as far as to utilise the metabolites released to the environment during apoptosis for their own growth. The primary emphasis of the field has been on the identification of what form of programmed cell death is initiated during infection and what the immunological consequences are. In contrast, less is known about how the critical stages of cell death and cell clearance directly or indirectly impact the microbes (both commensal and pathogenic) themselves. In this review, we will pay particular attention to the host cell-cell communication events occurring downstream of programmed cell death and highlight new research and new questions surrounding how these fundamental host processes interact with the bacterial communities, with a particular focus on the intestine and the lung.