Clostridial Gas Gangrene: Evidence That α and θ Toxins Differentially Modulate the Immune Response and Induce Acute Tissue Necrosis

• Published in: The Journal of infectious diseases 1997-07, Vol.176 (1), p.189-195
• Main Authors: Stevens, Dennis L., Tweten, Rodney K., Awad, Milena M., Rood, Julian I., Bryant, Amy E.
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Toxins - immunology; Bacterial Toxins - toxicity; Bacteriology; Biological and medical sciences; Calcium-Binding Proteins; Clostridium perfringens; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gas gangrene; Gas Gangrene - immunology; Gas Gangrene - pathology; Hemolysin Proteins; Immunization; Immunobiology; Infections; Major Articles; Mice; Microbiology; Modulation of the immune response (stimulation, suppression); Monoclonal antibodies; Mortality; Muscle tissues; Necrosis; Neutrophils; Neutrophils - physiology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Toxins; Transcriptional regulatory elements; Type C Phospholipases
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/514022

The rapid extension of necrosis and an absence of polymorphonuclear leukocytes (PMNL) at the site of infection are two hallmarks of Clostridium perfringens gas gangrene. While both a and u toxins profoundly affect PMNL function and viability in vitro, their roles in muscle destruction and impairment of the inflammatory response in vivo have not been investigated. Comparative histopathologic examinations were performed on animals infected with either wild-type C. perfringens, or isogenic, toxin-deficient mutants of C. perfringens. Tissue destruction was modest in animals infected with the α toxin-deficient mutant; destruction was more pronounced in tissues infected with the θ toxin-deficient mutant or the wild-type strain. α and θ toxins also displayed differing abilities to modulate the inflammatory response. Histopathologic studies in which recombinant toxins were injected together with killed, washed C. perfringens further substantiated these tissue-destructive and differential antiinflammatory effects.