A Farewell to Arms: Streptococcal Strategies to Cope with Innate Immunity

Herwald, Heiko; Egesten, Arne

doi:10.1159/000363749

Cited by 2 publications

(2 citation statements)

References 20 publications

(14 reference statements)

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“…The Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is an important human pathogen causing a variety of superficial infections of the skin (impetigo and erysipelas) and throat (pharyngitis) (9). Under rare and unfortunate circumstances, these complications can lead to severe life-threatening systemic infections, such as necrotizing fasciitis and streptococcal toxic shock syndrome, often associated with high rates of morbidity and mortality (10)(11)(12).…”

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confidence: 99%

Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein

et al. 2015

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The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a pathogen-associated molecular pattern to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal protein kinase and the subsequent induction and mobilization of the transcription factors NF-B and AP-1. We also determined the imprint of the inflammatory mediators released, such as interleukin-8 (IL-8), growth-related oncogene alpha, migration inhibitory factor, extracellular matrix metalloproteinase inducer, IL-1␣, IL-1 receptor a, and ST2, in response to streptococcal M1 protein. The expression of IL-8 is dependent on Toll-like receptor 2 activity and subsequent activation of the mitogen-activated protein kinases ERK and p38. Notably, this signaling seems to be distinct for IL-8 release, and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate in a proinflammatory manner in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein.

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Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein

et al. 2015

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“…acute rheumatic fever and invasive infections (27). The devastating conditions seen in many patients suffering from invasive infections, are to a great deal due to the capacity of the pathogen to modulate and avoid the host defense machinery (28,29). Notably, during disease progression, pathologic activation of coagulation and inflammation are known to trigger systemic complications.…”

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confidence: 99%

Active but inoperable thrombin is accumulated in a plasma protein layer surrounding Streptococcus pyogenes

Naudin¹,

Hurley²,

Malmström³

et al. 2015

Thromb Haemost

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Activation of thrombin is a critical determinant in many physiological and pathological processes including haemostasis and inflammation. Under physiological conditions many of these functions are involved in wound healing or eradication of an invading pathogen. However, when activated systemically, thrombin can contribute to severe and life-threatening conditions by causing complications such as multiple multi-organ failure and disseminated intravascular coagulation. In the present study we investigated how the activity of thrombin is modulated when it is bound to the surface of Streptococcus pyogenes. Our data show that S. pyogenes bacteria become covered with a proteinaceous layer when incubated with human plasma, and that thrombin is a constituent of this layer. Though the coagulation factor is found attached to the bacteria with a functional active site, thrombin has lost its capacity to interact with its natural substrates and inhibitors. Thus, the interaction of bacteria with human plasma renders thrombin completely inoperable at the streptococcal surface. This could represent a host defense mechanism to avoid systemic activation of coagulation which could be otherwise induced when bacteria enter the circulation and cause systemic infection.

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A Farewell to Arms: Streptococcal Strategies to Cope with Innate Immunity

Cited by 2 publications

References 20 publications

Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein

Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein

Active but inoperable thrombin is accumulated in a plasma protein layer surrounding Streptococcus pyogenes

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