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-alpha 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.
Epelman
Slava
S
Department of Microbiology and Infectious Diseases, Heritage Medical Research Building, 3330 Hospital Drive, University of Calgary, Calgary, Alberta, Canada, T2N-4N1.
Neely
Graham G
GG
Ma
Ling Ling
LL
Gjomarkaj
Mark
M
Pace
Elisabetta
E
Melis
Mario
M
Woods
Donald E
DE
Mody
Christopher H
CH
D036002:ADP Ribose Transferases / Q000276:immunology* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000276:immunology / Q000494:pharmacology; D001427:Bacterial Toxins; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D036002:ADP Ribose Transferases; C444820:exoenzyme S