Effects of Staphylococcal Enterotoxins on Human Neutrophil Functions and Apoptosis

Abstract

Staphylococcal enterotoxins have marked effects on the properties of T cells and monocytes and have recently been reported to affect neutrophil function. In this study, we investigated the abilities of staphylococcal enterotoxins A and B and toxic shock syndrome toxin 1 to affect respiratory burst activity and to delay apoptosis in human neutrophils. When cultures containing approximately 97% neutrophils were tested, the toxins all delayed neutrophil apoptosis in a dose-dependent manner and induced the expression of FcγRI on the neutrophil cell surface. These effects on apoptosis and expression of FcγRI were largely abrogated by the addition of a neutralizing anti-gamma interferon antibody. Similarly, the effects of these toxins on phorbol ester-induced chemiluminescence were decreased after neutralization of gamma interferon. These effects on neutrophil function were mimicked by the addition of conditioned medium from peripheral blood mononuclear cells incubated with the toxins, and again, neutralizing anti-gamma interferon antibodies largely negated the effects. However, when highly purified neutrophils prepared by immunodepletion of T cells and major histocompatibility complex class II-expressing cells were analyzed, the toxins were without effect on apoptosis and FcγRI expression, but granulocyte-macrophage colony-stimulating factor and gamma interferon could still delay apoptosis. These data indicate that these toxins have no direct effect on neutrophil apoptosis but can act indirectly via the production of T-cell-derived and monocyte-derived cytokines. It is noteworthy that such effects are detected in neutrophil suspensions containing only 3% contamination with T cells and other mononuclear cells.

Down-regulation of CXCR1 and CXCR2 expression on human neutrophils upon activation of whole blood byS. aureusis mediated by TNF-α

“…Our data demonstrate that SAC‐induced down‐regulation of CXCR1 and CXCR2 on neutrophils in whole blood and the total leucocyte fraction was abrogated by neutralizing antibody to TNF‐α, indicating that the effect was indirect and mediated via TNF‐α produced by other leucocyte subsets. These data are in agreement with the recent demonstration that the effects of staphylococcal toxins on neutrophil respiratory burst activity and apoptosis are indirect and completely mediated via monocyte and T‐cell‐derived cytokines, while purified neutrophils do not respond to the toxins [38]. It seems likely that isolated staphylococcal toxins [36,38], as well as killed SAC bacteria exposing a spectrum of cell‐wall staphylococcal toxins, have no direct effect on human neutrophils which do not express MHC‐II antigens.…”

Role of neutrophils in innate immunity: a systems biology‐level approach

“…Mononuclear cell-dependent enhancement of neutrophil survival has also been demonstrated following exposure to staphylococcal enterotoxins. 161 Several other bacterial molecules have been shown to directly promote neutrophil survival, such as E. coli verotoxin, 162 Shiga toxin, 163 and Sta. epidermidis PSMs.…”

Interferon‐γ activation of polymorphonuclear neutrophil function

“…117 Suppression of apoptosis was also correlated with other functions induced by IFN-c, such as FccRI expression and enhanced oxidative burst. 107,118 Similarly to what has been reported in other cell types, suppression of apoptosis in PMNs involved tyrosine-kinase dependent pathways. 117…”