Distinct fates of monocytes and T cells directly activated by Pseudomonas aeruginosa exoenzyme S

Gram‐negative infections can cause overwhelming inflammatory responses. Although factors other than LPS are clearly involved, these factors and their mechanisms of action have been poorly defined. During studies of LPS‐independent inflammatory responses of the gram‐negative pathogen Pseudomonas aeruginosa, an important virulence factor (exoenzyme S) was shown to be a potent mitogen for T cells. The current work demonstrates that exoenzyme S selectively induced transcription and secretion of biologically active cytokines and chemokines (chemotactic for neutrophils and T cells) from monocytes. Exoenzyme S stimulated highly purified monocytes independent of T cells. In addition, exoenzyme S stimulated T cells directly; neither T‐cell activation (CD69) nor apoptosis (hypodiploidy) required the presence of monocytes. However, T‐cell activation was enhanced via a noncontact‐dependent mechanism as a result of the secretion of TNF‐α and IL‐6. This study identifies a unique property of a gram‐negative‐derived microbial product capable of activating multiple cell types and suggests a mechanism by which exoenzyme S contributes to the immunopathogenesis of cystic fibrosis and sepsis in patients infected with P. aeruginosa.