Effects of staphylococci on cytokine production from human keratinocytes

Sasaki, Takayuki; Kano, Rui; Sato, Hiroko; Nakamura, Yuka; Watanabe, Shinichi; Hasegawa, Atsuhiko

doi:10.1046/j.1365-2133.2003.05017.x

Cited by 42 publications

(38 citation statements)

References 14 publications

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“…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)(8)(9)(10)(11). However, this stimulation requires the concurrent presence of a surfactant, such as SDS (11).…”

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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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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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“…Some authors had similar difficulties with the detection of TNF-a in the supernatants of unstimulated cultured human keratinocytes by ELISA [30,31]. Treatment with staphylococcal enterotoxin B, all-trans-retinoic acid, phorbol-myristateacetate and 10 mJ/cm 2 UVB resulted in the appearance of a small amount of TNF-a (6-25 pg/ml) detectable by ELISA in the supernatants of cultured keratinocytes [31,32].…”

Section: Discussionmentioning

confidence: 95%

“…It is also known that LPS used in the range of 0.1-10 Ag/ml can induce the IL-8 production of human keratinocytes [30]. Tacrolimus was shown to decrease the viability of normal human keratinocytes over 1000 nM concentration [25,26].…”

Section: Discussionmentioning

confidence: 99%

Budesonide, but not tacrolimus, affects the immune functions of normal human keratinocytes

Kis

Bodai

Polyánka

et al. 2006

International Immunopharmacology

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“…Cutaneous innate immune cells (Blander and Medzhitov, 2004), keratinocytes, and even melanocytes (Stadnyk, 1994;Takashima and Bergstresser, 1996) are all capable of producing innate cytokines, such as IL-6. Indeed, in AD, where keratinocytes act as a critical first line of defense against microbes, early IL-6 production has been described after direct contact of keratinocytes with S. aureus (Sasaki et al, 2003). Moreover, IL-6 has been found to be increased in AD skin (Fedenko et al, 2011) and especially in AD skin lesions (Travers et al, 2010), in which the amount of IL-6 correlates with bacterial burden (Travers et al, 2010).…”

Section: Discussionmentioning

confidence: 97%

Cutaneous Innate Immune Sensing of Toll-like Receptor 2-6 Ligands Suppresses T Cell Immunity by Inducing Myeloid-Derived Suppressor Cells

et al. 2014

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Skin is constantly exposed to bacteria and antigens, and cutaneous innate immune sensing orchestrates adaptive immune responses. In its absence, skin pathogens can expand, entering deeper tissues and leading to life-threatening infectious diseases. To characterize skin-driven immunity better, we applied living bacteria, defined lipopeptides, and antigens cutaneously. We found suppression of immune responses due to cutaneous infection with Gram-positive S. aureus, which was based on bacterial lipopeptides. Skin exposure to Toll-like receptor (TLR)2-6-binding lipopeptides, but not TLR2-1-binding lipopeptides, potently suppressed immune responses through induction of Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs). Investigating human atopic dermatitis, in which Gram-positive bacteria accumulate, we detected high MDSC amounts in blood and skin. TLR2 activation in skin resident cells triggered interleukin-6 (IL-6), which induced suppressive MDSCs, which are then recruited to the skin suppressing T cell-mediated recall responses such as dermatitis. Thus, cutaneous bacteria can negatively regulate skin-driven immune responses by inducing MDSCs via TLR2-6 activation.

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Effects of staphylococci on cytokine production from human keratinocytes

Abstract: These results could explain the epidermal infiltration of neutrophils in cutaneous infection with staphylococci, suggesting that the analysis of cytokines might add valuable information for the pathogenesis of cutaneous infection with Staphylococcus species.

Cited by 42 publications

References 14 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

Budesonide, but not tacrolimus, affects the immune functions of normal human keratinocytes

Cutaneous Innate Immune Sensing of Toll-like Receptor 2-6 Ligands Suppresses T Cell Immunity by Inducing Myeloid-Derived Suppressor Cells

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