Dataset Information

Systemic cytokine and chemokine responses in immunized mice challenged with staphylococcal enterotoxin B.

ABSTRACT: The cytokine storm induced by staphylococcal enterotoxin B (SEB) describes the rapid and dramatic induction of mediators which are likely responsible for the toxin's deleterious effects. However despite the use of numerous animal models for investigating SEB related illness in humans, mechanisms of toxicity and correlates of protection remain unclear. In the present study, we used an LPS-potentiated model of SEB lethality to investigate the toxin-induced cytokine and chemokine responses in untreated and immunized mice. Of 30 separate mediators analyzed, serum levels for 28 or 27 of these cytokines and chemokines were elevated following administration of dosages of 3 or 30 LD50 of native SEB, respectively. Mice immunized with a non-toxic SEB vaccine candidate expressed in either E. coli or transgenic soy expression systems were protected from lethality when challenged with potentiated SEB. The majority of SEB-induced cytokines and chemokines (21 of 28 or 23 of 27 following challenge with dosages of 3 or 30 LD50 of native SEB, respectively) were significantly decreased in mice immunized with an SEB vaccine candidate when compared to control animals. Together, these studies provide the most comprehensive evaluation of the cytokine storm induced in this LPS-potentiated model of SEB lethality to date. As with other animal models, the identification of those mediators which are necessary and sufficient for SEB-induced toxicity remains unclear.

SUBMITTER: Hudson Reichenberg LC

PROVIDER: S-EPMC5534135 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systemic cytokine and chemokine responses in immunized mice challenged with staphylococcal enterotoxin B.

Hudson Reichenberg Laura C LC Garg Renu R Fernalld Raymond R Bost Kenneth L KL Piller Kenneth J KJ

Toxicon : official journal of the International Society on Toxinology 20170503

The cytokine storm induced by staphylococcal enterotoxin B (SEB) describes the rapid and dramatic induction of mediators which are likely responsible for the toxin's deleterious effects. However despite the use of numerous animal models for investigating SEB related illness in humans, mechanisms of toxicity and correlates of protection remain unclear. In the present study, we used an LPS-potentiated model of SEB lethality to investigate the toxin-induced cytokine and chemokine responses in untre ...[more]

PMID: 28478060

Similar Datasets

Project description:Toxic shock syndrome (TSS) is capable of inducing life-threatening fever, rash, and systemic organ failure, though the specific mechanisms behind these symptoms remain poorly understood. Staphylococcal enterotoxin B (SEB) and other superantigens have shown to be important factors in TSS, capable of promoting cross-linking between T cell receptors and major histocompatibility complexes which results in overwhelming T cell activation, proliferation, and cytokine production. The resulting proinflammatory cytokine cascade, often referred to as the "cytokine storm," seems to be critical to the development of disease. Interestingly, clinical studies have shown that children exhibit less severe TSS-associated morbidity than adults, though the mechanism behind this phenomenon has not been addressed. Indeed, despite the fact that most novel antigen exposure occurs early in life, be it from environmentally acquired pathogens or routine vaccination, normal pediatric T cell immune functions remain critically underexplored. This is largely due to difficulty in obtaining enough samples to explore more than a narrow sliver of the cell-mediated immune compartment. To address this limitation, we optimized a T effector (Teff)/circulating T follicular helper (cTFH) cell mass cytometry panel which allowed us to analyze a wide array of T cell populations and effector functions following in vitro SEB stimulation. We show that T cell activation-as measured by CD69 expression-following SEB stimulation is lower in pediatric participants, increasing throughout childhood, and reaching adult levels by around 15?years old. Further, while individual CD4+ effector memory T cell (TEM) effector molecules show limited age-associated differences following SEB stimulation, multifunctional CD4+ TEM are shown to positively correlate with increasing age through adolescence. Individual CD8+ TEM effectors and multifunctional phenotypes also show very strong age-associated increases following SEB stimulation. SEB stimulation has little impact on cTFH activation or functional cellular markers, regardless of age. These results, coupled with the fact that a robust proinflammatory cytokine response seems critical to developing severe TSS, suggest a possible connection between the significantly reduced T cell activation and multifunctional populations following in vitro SEB stimulation in our pediatric participants and clinical observations relating to reduced TSS mortality in children.

Dataset Information

Systemic cytokine and chemokine responses in immunized mice challenged with staphylococcal enterotoxin B.

Publications

Systemic cytokine and chemokine responses in immunized mice challenged with staphylococcal enterotoxin B.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets