Bacterial pyrogenic exotoxins as superantigens

Abstract

The recent discovery of the mode of interaction between a group of microbial proteins known as superantigens and the immune system has opened a wide area of investigation into the possible role of these molecules in human diseases. Superantigens produced by certain viruses and bacteria, including Mycoplasma species, are either secreted or membrane-bound proteins. A unique feature of these proteins is that they can interact simultaneously with distinct receptors on different types of cells, resulting in enhanced cell-cell interaction and triggering a series of biochemical reactions that can lead to excessive cell proliferation and the release of inflammatory cytokines. However, although superantigens share many features, they can have very different biological effects that are potentiated by host genetic and environmental factors. This review focuses on a group of secreted pyrogenic toxins that belong to the superantigen family and highlights some of their structural-functional features and their roles in diseases such as toxic shock and autoimmunity. Deciphering the biological activities of the various superantigens and understanding their role in the pathogenesis of microbial infections and their sequelae will enable us to devise means by which we can intervene with their activity and/or manipulate them to our advantage.

Host variation in cytokine responses to superantigens determine the severity of invasive group A streptococcal infection

“…The frequencies of inflammatory cytokineproducing cells found in the circulation of patients with severe invasive GAS infections, which reached above 20% for a single cytokine in some STSS patients, corresponded well to frequencies expected for a superantigen response (5-40%). This provides further support for the proposed central role of streptococcal superantigens in the pathogenesis of severe invasive GAS disease [4][5][6][7]. Furthermore, these findings are in agreement with a recent study by Arad et al [31], which showed that inhibition of superantigen induced cytokine expression by peptide antagonist protected mice against toxic shock.…”

“…Superantigens produced by GAS are believed to be central mediators of the systemic effects seen in severe invasive GAS disease (reviewed in [4][5][6][7]). GAS express several different antigens and superantigens capable of eliciting cytokine responses and activating a large proportion of immune cells (reviewed in [4,5,7]).…”

“…GAS express several different antigens and superantigens capable of eliciting cytokine responses and activating a large proportion of immune cells (reviewed in [4,5,7]). Superantigens typically induce a massive T helper 1 cytokine responses in human mononuclear cells with no or very low level of T helper 2 cytokines [8][9][10][11][12].…”

Staphylokokken-Enterotoxine: Bildung, Eigenschaften und Nachweis

“…Während die SE Superantigencharakter aufweisen, also in der Lage sind, T-Zellen unspezifi sch zu aktivieren (Polyklonale T-Zellen-Stimulation mit Zytokin-und Mediatorenausschüt-tung sowie Gerinnungs-, Komplement-und Plättchenaktivie-rung, wodurch die Endothelzellen geschädigt, der periphere Gefäßwandwiderstand gemindert und Kapillarleckagen mit septischem Schock und Immunsuppression initiiert werden) (Marrack und Kappler, 1990;Fleischer, 1995;Kotb, 1995;Müller-Alouf et al, 2001;Baker und Archarya, 2004), haben trotz ihres Namens nicht alle SE auch Enterotoxincharakter. Um dies in der Nomenklatur der Toxine deutlich zu machen und um Mißverständnissen vorzubeugen, schlug das International Nomenclature Committee for Staphylococcal Superantigens (INCSS) folgende Regeln für die Bezeichnung neu beschriebener bzw.…”

Zweimaliges toxisches Schocksyndrom

“…Der Nachweis von Staphylococcus aureus oder des Toxins (Toxic-shock-Syndrom-Toxin-1) gelingt jedoch nicht in allen Fällen. Die Wirkungsweise des Toxic-shock-Syndrom-Toxin-1 ist gut erforscht [4,8] …”