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

R.M. ORTIZ FLORES ; C.S. C´ACERES; T.I. CORTINAS; S.E. GOMEZ MEJIBA ; C.V. SASSO ; D. C. RAMIREZ ; M.A. MATTAR DOMÍNGUEZ

TOXICON

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2024

0041-0101

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