Early kinetics of the transcriptional response of human leukocytes to staphylococcal superantigenic enterotoxins A and G.
The severity of Staphylococcus aureus sepsis is positively associated with staphylococcal enterotoxin A (SEA) and negatively associated with the enterotoxin gene cluster (egc), which encodes five staphylococcal enterotoxins (SE). It was recently demonstrated that SE can induce human leukocytes to release inflammatory mediators. Contrary to SEG (one of the five egc superantigens), SEA induces a strong proinflammatory/Th1 response, including tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha production. Here, we investigated the very early transcriptional response of human PBMC to these two SEs. We confirm that SEA is more potent than SEG. Importantly, our data also suggest that the early response to SE is likely induced more by T cells than by monocytes. In addition, negative feedback control is triggered at the same time as proinflammatory processes (inflammation and apoptosis). It confirms at the molecular level new models of sepsis pathophysiology as concomitant and opposite sides of a given mechanism participating to response to bacterial compound are both necessary. This preliminary study highlights the potential of transcriptional studies for unraveling the very early mechanisms of leukocyte responses to SE. Further studies are needed to understand the mechanisms underlying the putative synergy between SE and other bacterial components.
Dauwalder
Olivier
O
Université Lyon, France.
Pachot
Alexandre
A
Cazalis
Marie Angélique
MA
Paye
Malick
M
Faudot
Caroline
C
Badiou
Cédric
C
Mougin
Bruno
B
Vandenesch
François
F
Etienne
Jerome
J
Lina
Gerard
G
Monneret
Guillaume
G
D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000276:immunology*; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D014158:Transcription, Genetic
D016207:Cytokines; D004768:Enterotoxins; D018089:Superantigens; C419397:enterotoxin G, staphylococcal; C026066:enterotoxin A, Staphylococcal