Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation

Påhlman, Lisa I.; Olin, Anders I.; Darenberg, Jessica; Mörgelin, Matthias; Kotb, Malak; Herwald, Heiko; Norrby‐Teglund, Anna

doi:10.1111/j.1462-5822.2007.01053.x

Cited by 37 publications

(46 citation statements)

References 59 publications

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“…Thus, bacterial triggers other than the classical sepsis-associated bacterial factors LPS and superantigen must be involved. One likely candidate was the streptococcal M1 protein that has recently received a lot of attention due to its immunostimulatory activity (18,26,27). Most pertinent to this study is its role as a mediator of potent activation and degranulation of neutrophils that result in vascular leakage and septic shock as well as acute lung injury (21,26).…”

Section: Discussionmentioning

confidence: 99%

“…Supernatants were also prepared from cultures of the AP1 strain and its isogenic mutant MC25, which contains a truncated form of the M1 protein that lacks the transmembrane-spanning region, leading to M1 protein accumulation in the supernatant (17). The M1 protein was purified from the AP1-derived strain MC25 as described (18).…”

Section: Bacterial Strains and Factorsmentioning

confidence: 99%

“…The two cohorts were well matched with respect to age, gender, and severity of infection based on a sepsis-associated organ failure assessment (SOFA) score at the day of enrollment in the study (STSS: median 11.50, range 6 -19; G-negative cohort: median 13.00, range [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Analyses of systemic resistin levels confirmed our previous finding (5) that septic shock patients have markedly elevated levels (28-fold higher) as compared with healthy controls ( p Ͻ 0.0001) (Fig.…”

Section: Persistent Systemic Hyperresistinemia In Stss Patientsmentioning

confidence: 99%

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Neutrophil-Derived Hyperresistinemia in Severe Acute Streptococcal Infections

Johansson

Linnér

Sundén-Cullberg

et al. 2009

The Journal of Immunology

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The concept of neutrophil activation and degranulation as important contributors to disease pathology in invasive group A streptococcal infections has recently been emphasized. This study focuses on two of the most severe streptococcal manifestations, toxic shock syndrome and necrotizing fasciitis, and the newly described proinflammatory molecule resistin, known to derive from adipocytes and monocytes. We demonstrate for the first time that these conditions are characterized by hyperresistinemia in circulation as well as at the local site of infection. Importantly, analyses of patient tissue biopsies and whole blood revealed that neutrophils represent a novel and dominant source of resistin in bacterial septic shock. This was confirmed by the identification of resistin within neutrophil azurophilic granules. In vitro assays using primary neutrophils showed that resistin release was readily triggered by streptococcal cell wall components and by the streptococcal M1 protein, but not by the potent streptococcal superantigens. This is the first report demonstrating that resistin is released from neutrophils in response to microbial stimuli, which adds resistin to the neutrophil granule proteins that are likely to contribute to the pathologic inflammatory responses associated with severe streptococcal infections.

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Section: Discussionmentioning

confidence: 99%

Section: Bacterial Strains and Factorsmentioning

confidence: 99%

Section: Persistent Systemic Hyperresistinemia In Stss Patientsmentioning

confidence: 99%

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Neutrophil-Derived Hyperresistinemia in Severe Acute Streptococcal Infections

Johansson

Linnér

Sundén-Cullberg

et al. 2009

The Journal of Immunology

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“…However, it is also possible that the molecule has superantigen activity due to regions of the protein not involved in protease activity. There is precedent for this to occur, as another protein, streptococcal M protein, has both recognized antiphagocytic and superantigen activities (72,73). It thus seems likely that the protein is both a cysteine protease and an atypical superantigen.…”

Section: The Superantigen Familymentioning

confidence: 99%

Staphylococcal and Streptococcal Superantigen Exotoxins

et al. 2013

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SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies.

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“…Soluble M1 protein released from S. pyogenes is a potent inducer of T-cell proliferation and the release of Th1-type cytokines. This leads to the suggestion that it is also a novel streptococcal superantigen contributing to excessive T-cell activation and inflammatory responses during invasive streptococcal infections (445). The pathological inflammatory response is believed to be enhanced by IgG antibodies to the C repeats ( AgI/II polypeptides.…”

Section: Cell Wall-anchored Polypeptidesmentioning

confidence: 99%

StreptococcusAdherence and Colonization

Nobbs

Lamont

Jenkinson

2009

Microbiol Mol Biol Rev

552

569

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SUMMARY Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed.

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Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation

Cited by 37 publications

References 59 publications

Neutrophil-Derived Hyperresistinemia in Severe Acute Streptococcal Infections

Neutrophil-Derived Hyperresistinemia in Severe Acute Streptococcal Infections

Staphylococcal and Streptococcal Superantigen Exotoxins

StreptococcusAdherence and Colonization

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