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

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. Key Contribution:There is growing evidence for an involvement of S. aureus SAgs in allergies. Colonization with S. aureus and the presence of IgE antibodies against SAgs (also known as SE-IgE) are strongly linked with allergic sensitization and severe chronic inflammatory airway diseases. Here, we discuss possible mechanisms by which SAgs can drive/or exacerbate an allergic immune response.

T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion

“…Such a physical interaction between TCRs and SAgs, which exists outside of the peptide-binding groove, involves a large number of TRBV region genes that are targeted in distinct patterns by bacterial SAgs [ 39 , 255 ]. At present, 26 different SAgs from S. aureus are described, comprising toxic shock syndrome toxin-1 (TSST-1), 11 SEs (SEA–SEE, SEG–SEI, SER–SET), and 14 SE-like (SEl) proteins (SElJ–SElQ, SElU–SElZ) [ 256 , 257 ]. There are also 14 Streptococcal pyrogenic exotoxins (Spe), which include SpeA, SpeC, SpeG, SpeH, streptococcal mitogenic exotoxin Z, and streptococcal superantigen A [ 258 ].…”

Modulation of Allergic Sensitization and Allergic Inflammation by Staphylococcus aureus Enterotoxin B in an Ovalbumin Mouse Model

“…Also patients with chronic rhinosinusitis are frequently colonized by S. aureus (16,47) and a significant relationship between nasal S. aureus carriage and asthma severity has been recognized (8). Different S. aureus proteins, such as, e.g., serine protease like proteases (Spls), have come into focus regarding Th2-biased immune responses (48) and also S. aureus toxins have been proposed to contribute to the development of allergic diseases in clinical and experimental studies (49,50). Clinical studies analyzing S. aureus isolates recovered from nasal carriers showed occurrence of SEB-producing strains (51, 52), whereas to our knowledge reports on natural concentrations of SEB produced by S. aureus in the human respiratory tract are lacking.…”

Epidemiological and Clinical Evidence for the Role of Toxins in S. aureus Human Disease

“…A study focusing on infective endocarditis and sepsis in rabbits found that, when rabbits were infected with strains lacking sec , they were less susceptible to kidney infection and death [ 113 ]. Interestingly, S. aureus enterotoxins have also been implicated in allergic syndromes such as atopic dermatitis (AD), a chronic inflammatory disease of the skin [ 114 ]. Over 80% of individuals with AD are also colonized with S. aureus in some studies [ 115 , 116 ], and as many as 65% of S. aureus strains isolated from AD patients express enterotoxins [ 116 , 117 , 118 ].…”