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      Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus?

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          Abstract

          Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive cytokine release. To date, 26 different SAgs have been described in the species S. aureus; they comprise the toxic shock syndrome toxin (TSST-1), as well as 25 staphylococcal enterotoxins (SEs) or enterotoxin-like proteins (SEls). SAgs can cause staphylococcal food poisoning and toxic shock syndrome and contribute to the clinical symptoms of staphylococcal infection. In addition, there is growing evidence that SAgs are involved in allergic diseases. This review provides an overview on recent epidemiological data on the involvement of S. aureus SAgs and anti-SAg-IgE in allergy, demonstrating that being sensitized to SEs—in contrast to inhalant allergens—is associated with a severe disease course in patients with chronic airway inflammation. The mechanisms by which SAgs trigger or amplify allergic immune responses, however, are not yet fully understood. Here, we discuss known and hypothetical pathways by which SAgs can drive an atopic disease.

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          Most cited references114

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          Reclassification of Staphylococcus aureus nasal carriage types.

          Persistent nasal carriers have an increased risk of Staphylococcus aureus infection, whereas intermittent carriers and noncarriers share the same low risk. This study was performed to provide additional insight into staphylococcal carriage types. Fifty-one volunteers who had been decolonized with mupirocin treatment and whose carriage state was known were colonized artificially with a mixture of S. aureus strains, and intranasal survival of S. aureus was compared between carriage groups. Antistaphylococcal antibody levels were also compared among 83 carriage-classified volunteers. Persistent carriers preferentially reselected their autologous strain from the inoculum mixture (P=.02). They could be distinguished from intermittent carriers and noncarriers on the basis of the duration of postinoculation carriage (154 vs. 14 and 4 days, respectively; P=.017, by log-rank test). Cultures of swab samples from persistent carriers contained significantly more colony-forming units per sample than did cultures of swab samples from intermittent carriers and noncarriers (P=.004). Analysis of serum samples showed that levels of immunoglobulin G and immunoglobulin A to 17 S. aureus antigens were equal in intermittent carriers and noncarriers but not in persistent carriers. Along with the previously described low risk of infection, intermittent carriers and noncarriers share similar S. aureus nasal elimination kinetics and antistaphylococcal antibody profiles. This implies a paradigm shift; apparently, there are only 2 types of nasal carriers: persistent carriers and others. This knowledge may increase our understanding of susceptibility to S. aureus infection.
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            The biology of IGE and the basis of allergic disease.

            Allergic individuals exposed to minute quantities of allergen experience an immediate response. Immediate hypersensitivity reflects the permanent sensitization of mucosal mast cells by allergen-specific IgE antibodies bound to their high-affinity receptors (FcepsilonRI). A combination of factors contributes to such long-lasting sensitization of the mast cells. They include the homing of mast cells to mucosal tissues, the local synthesis of IgE, the induction of FcepsilonRI expression on mast cells by IgE, the consequent downregulation of FcgammaR (through an insufficiency of the common gamma-chains), and the exceptionally slow dissociation of IgE from FcepsilonRI. To understand the mechanism of the immediate hypersensitivity phenomenon, we need explanations of why IgE antibodies are synthesized in preference to IgG in mucosal tissues and why the IgE is so tenaciously retained on mast cell-surface receptors. There is now compelling evidence that the microenvironment of mucosal tissues of allergic disease favors class switching to IgE; and the exceptionally high affinity of IgE for FcepsilonRI can now be interpreted in terms of the recently determined crystal structures of IgE-FcepsilonRI and IgG-FcgammaR complexes. The rate of local IgE synthesis can easily compensate for the rate of the antibody dissociation from its receptors on mucosal mast cells. Effective mechanisms ensure that allergic reactions are confined to mucosal tissues, thereby minimizing the risk of systemic anaphylaxis.
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              The bacterial superantigen and superantigen-like proteins.

              The bacterial superantigens are protein toxins that bind to major histocompatibility complex class II and T-cell receptor to stimulate large numbers of T cells. The majority are produced by the Gram-positive organisms Staphylococcus aureus and Streptococcus pyogenes and are the causative agents in toxic shock syndrome, an acute disease caused by the sudden and massive release of T-cell cytokines into the blood stream. The structure and function of the superantigens has revealed a common architecture that is also shared by another group of staphylococcal virulence factors called the superantigen-like proteins (SSL). Together, this family of structurally related molecules highlights how a common pathogenic organism has employed a simple but adaptable protein to generate an armamentarium of potent defense molecules designed to target of the innate and adaptive immune response.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                12 March 2020
                March 2020
                : 12
                : 3
                : 176
                Affiliations
                [1 ]Department of Immunology, University Medicine Greifswald, 17475 Greifswald, Germany; goran.abdurrahman@ 123456uni-greifswald.de (G.A.); frieder.schmiedeke@ 123456uni-greifswald.de (F.S.); broeker@ 123456uni-greifswald.de (B.M.B.)
                [2 ]Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, 9000 Ghent, Belgium; Claus.Bachert@ 123456UGent.be
                [3 ]Current address: Department of Medicine Solna, Immunology and Allergy Research Unit, Karolinska Institute, 171 77 Stockholm, Sweden
                Author notes
                [* ]Correspondence: silva.holtfreter@ 123456med.uni-greifswald.de ; Tel.: +49-3834-86-5518
                Author information
                https://orcid.org/0000-0001-6958-7936
                https://orcid.org/0000-0002-5020-8542
                https://orcid.org/0000-0002-2672-8230
                Article
                toxins-12-00176
                10.3390/toxins12030176
                7150838
                32178378
                a70fac93-a0ab-49dd-8b79-1fd19e2c9447
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 February 2020
                : 10 March 2020
                Categories
                Review

                Molecular medicine
                staphylococcus aureus,superantigens,t cells,allergy,sensitization,ige,t cell superallergen

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