Role of the Inflammasome, IL-1<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:math>, and IL-18 in Bacterial Infections

Sahoo, Manoranjan; Ceballos-Olvera, Ivonne; Barrio, Laura; Re, Fabio

doi:10.1100/2011/212680

Cited by 222 publications

(147 citation statements)

References 98 publications

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“…Caspase 1 activation can also result in the activation of the proinflammatory cytokine IL-1␤ (17). These mature cytokines are then released from the cell and have varied effects, such as leukocyte recruitment, promotion of T and B cell activation, and upregulation of other inflammatory cytokines (18).…”

mentioning

confidence: 99%

Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation

et al. 2015

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Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuous, it has strong associations with atopic dermatitis pathogenesis and has become the leading cause of skin and soft tissue infections in the United States. The factors that dictate the role of S. aureus in disease are still being determined. In this work, we utilized primary keratinocyte culture and an epidermal murine colonization model to investigate the role of S. aureus phenol-soluble modulins (PSMs) in proinflammatory cytokine release and inflammation induction. We demonstrated that many species of Staphylococcus are capable of causing release of interleukin 18 (IL-18) from keratinocytes and that S. aureus PSMs are necessary and sufficient to stimulate IL-18 release from keratinocytes independently of caspase 1. Further, after 7 days of epicutaneous exposure to wild-type S. aureus, but not S. aureus ⌬psm, we saw dramatic changes in gross pathology, as well as systemic release of proinflammatory cytokines. This work demonstrates the importance of PSM peptides in S. aureus-mediated inflammatory cytokine release from keratinocytes in vitro and in vivo and further implicates PSMs as important contributors to pathogenesis. Staphylococcus aureus is a human commensal that lives in the nose, skin, and throat in approximately 30% of the human population (1, 2). While S. aureus is usually harmless, it is an opportunistic pathogen that has become a leading cause of nosocomial infections in the United States (3) and can manifest as skin and soft tissue infections, infective endocarditis, osteomyelitis, and sepsis (1). Further, it has a role in exacerbation of atopic dermatitis (AD), a chronic inflammatory disease of the skin that affects up to 20% of children and up to 3% of adults (4, 5). Chronic cutaneous inflammation during AD results in increased production of extracellular matrix components that permit attachment of S. aureus (6). Subsequently, S. aureus promotes AD by stimulating a strong proinflammatory response (7). S. aureus proteins, such as hemolysin ␣ (HLA), staphylococcal protein A (SPA), and lipoteichoic acids (LTA), promote proinflammatory cytokine production from keratinocytes (7-11). However, this stimulation requires the concurrent presence of a surfactant, such as SDS (11).Keratinocytes serve as the first line of defense against cutaneous pathogens and are able to stimulate an immune response by releasing cytokines, defensins, and antimicrobial cationic peptides, such as LL-37, to fight off pathogens (12). One cytokine that is produced by keratinocytes and has a role in promoting AD is interleukin 18 (IL-18) (13,14). IL-18 is a proinflammatory cytokine that is cleaved and activated primarily by caspase 1 (15). Caspase 1 activation occurs following exposure to danger-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs), which stimulate the activation of the inflammasome (16). Caspase 1 activation can also result in the activation of the proinflammatory cytokine IL-1␤ (17)...

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confidence: 99%

Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation

et al. 2015

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“…L'interleukine-1b L'IL-1 est une cytokine majeure de la réponse inflammatoire, connue auparavant sous la dénomi-nation de pyrogène endogène [30,31]. Elle exerce de nombreuses fonctions comme l'induction de la fièvre au niveau cérébral ou la stimulation de la moelle osseuse à l'origine d'hyperleucocytose et de thrombocytose.…”

Section: Les Interleukines Pro-inflammatoiresunclassified

Les inflammasomes

Jamilloux

Henry

2013

Med Sci (Paris)

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“…NLRP3 and ASC mediate H. ducreyi-induced inflammasome activation. Bacterial pathogens induce the assembly of several types of inflammasomes (22,34,(42)(43)(44). The NLRP3 inflammasome is the most versatile type, sensing diverse microbial components as well as danger signals associated with tissue damage, and plays a crucial role in response to different bacterial infections (45).…”

Section: Transcriptional Activation Of Inflammasome-related Genes In Hmentioning

confidence: 99%

Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

Katz

Bauer

et al. 2013

Infect Immun

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Recognition of microbial infection by certain intracellular pattern recognition receptors leads to the formation of a multiprotein complex termed the inflammasome. Inflammasome assembly activates caspase-1 and leads to cleavage and secretion of the proinflammatory cytokines interleukin-1 beta (IL-1␤) and IL-18, which help control many bacterial pathogens. However, excessive inflammation mediated by inflammasome activation can also contribute to immunopathology. Here, we investigated whether Haemophilus ducreyi, a Gram-negative bacterium that causes the genital ulcer disease chancroid, activates inflammasomes in experimentally infected human skin and in monocyte-derived macrophages (MDM). Although H. ducreyi is predominantly extracellular during human infection, several inflammasome-related components were transcriptionally upregulated in H. ducreyi-in-

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Role of the Inflammasome, IL-1β, and IL-18 in Bacterial Infections

Cited by 222 publications

References 98 publications

Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation

Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation

Les inflammasomes

Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

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