Exotoxins secreted by Clostridium septicum induce macrophage death: Implications for bacterial immune evasion mechanisms at infection sites

The induction of macrophage death is considered a potential mechanism by which components secreted by Clostridium septicum are used to evade the innate immune response and cause tissue damage. This study aimed to determine the effects of partially purified fractions of extracellular proteins secreted by C. septicum on the death of mouse peritoneal macrophages. Elicited mouse peritoneal macrophages were incubated with partially purified fractions of proteins secreted by C. septicum into the culture medium. After incubation, the protein fraction with a molecular weight ≥100 kDa caused significant cell death in macrophages, altered cell morphology, increased the expression of markers of apoptosis and autophagy, and increased the expression (protein and mRNA) of IL-10 and TNFα. Our data suggest that the proteins secreted by C. septicum (MW, ≥100 kDa) induce cell death in macrophages by promoting autophagy-triggered apoptosis. This study may contribute to our understanding of the molecular mechanism of immune evasion by C. septicum at the infection site.