When The Sentinels Fall: Macrophage Cell Death Response to GAS Infection

Abstract: Group A Streptococcus (GAS) is a globally disseminated pathogen that causes >500,000 deaths yearly and is ranked as ninth leading infectious cause of human mortality by the World Health Organisation. The spectrum of disease ranges from superficial infections of the skin and epithelium to invasive and systemic infections. Although the interaction of GAS with neutrophils has been extensively studied much remains to be discovered about the role of macrophages, which are the first line of defence encountered by invading pathogens. In this study, the aim was to establish a means of deriving macrophages from primary monocytes and to study both the efficiency of macrophage killing of GAS and the macrophage cell death response to GAS infection. Here, we report that monocyte-derived macrophages are able to take up and kill GAS during in vitro infection. Production of reactive oxygen species by macrophages was elicited during infection, but not nearly in as high amounts as produced by neutrophils. Investigating the type of cell death induced by GAS, markers for both apoptosis and necroptosis can be found after 8 hours of infection. These results highlight that macrophages indeed are participating in the clearance of GAS and more studies are needed to understand the roles of macrophages in early control of GAS infection.