Molecular Characterization of Inflammation and Staphylococcus aureus Colonization of Involved Skin of Atopic Dermatitis Patients (original) (raw)
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Expression of Staphylococcus aureus Virulence Factors in Atopic Dermatitis
JID Innovations
Atopic dermatitis (AD) is a skin inflammatory disease in which the opportunistic pathogen Staphylococcus aureus is prevalent and abundant. S. aureus harbors several secreted virulence factors that have well-studied functions in infection models, but it is unclear whether these extracellular microbial factors are relevant in the context of AD. To address this question, we designed a culture-independent method to detect and quantify S. aureus virulence factors expressed at the skin sites. We utilized RNase-H-dependent multiplex PCR for preamplification of reverse-transcribed RNA extracted from tape strips of patients with AD sampled at skin sites with differing severity and assessed the expression of a panel of S. aureus virulence factors using qPCR. We observed an increase in viable S. aureus abundance on sites with increased severity of disease, and many virulence factors were expressed at the AD skin sites. Surprisingly, we did not observe any significant upregulation of the virulence factors at the lesional sites compared with those at the nonlesional control. Overall, we utilized a robust assay to directly detect and quantify viable S. aureus and its associated virulence factors at the site of AD skin lesions. This method can be extended to study the expression of skin microbial genes at the sites of various dermatological conditions.
Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis
Toxins
Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease.
STAPHYLOCOCCUS AUREUS AND ATOPIC DERMATITIS: WHICH CAME FIRST, THE CHICKEN OR THE EGG
Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease that affects up to 25% of children and 10% of adults. Approximately 90% of patients with AD are colonised by Staphylococcus aureus, compared with only 5-30% of non-atopic individuals. Th2 cytokines have a permissive effect on microbial invasion, the epidermal barrier, and cell-mediated immunity, which lowers the production of antimicrobial proteins. Superantigen-producing S. aureus colonisation is correlated with serum interleukin (IL)-4 levels. Up to 50-60% of the S. aureus found on patients with AD is toxin-producing. 1 S. aureus colonisation, infection, and production of toxins and superantigens is believed to drive, at least in part, the pathogenesis of AD. S. aureus mechanically disrupts epidermal integrity through protease activity, and also has the ability to be internalised by keratinocytes in which it activates the inflammasome and induces apoptosis. Some patients with AD produce specific immunoglobulin E (IgE) antibodies directed against staphylococcal superantigens to an extent that correlates with skin disease severity. IL-4 and IL-13 have also been reported to increase staphylococcal α-toxin-induced keratinocyte death via STAT6 signalling. The S. aureus superantigens staphylococcal enterotoxin B and toxic shock syndrome toxin 1 promote lymphocyte IL-31 production in patients with AD. IL-31 has, in turn, been shown to reduce filaggrin expression and mediate pro-inflammatory cytokine excretion, as well as induce toxin-specific IgE and basophilic activation. The ability of S. aureus to colonise skin affected by AD, and to activate and maintain a Th2 environment allowing, via the destruction of tight junctions, exposure to allergens and thus causing allergic sensitisation, makes it one of the main protagonists of the 'atopic march'.
Journal of Allergy and Clinical Immunology, 2016
Sciences (grant no. UL1TR000039), and Arkansas Biosciences Institute (to R.C.K.). S.S.A has salary support from CEGIR (U54 AI117804) which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, and NCATS, funded by AI114585 (to T.A.D.). Disclosure of potential conflict of interest: E. Tkachenko owns stock in MuWells Inc (supplier of elastic cell substrates
Immunomodulatory Role of Staphylococcus aureus in Atopic Dermatitis
Pathogens, 2022
Staphylococcus aureus is a gram-positive bacterium commonly found on humans, and it constitutes the skin microbiota. Presence of S. aureus in healthy individuals usually does not pose any threat, as the human body is equipped with many mechanisms to prevent pathogen invasion and infection. However, colonization of S. aureus has been correlated with many healthcare-associated infections, and has been found in people with atopic diseases. In atopic dermatitis, constant fluctuations due to inflammation of the epidermal and mucosal barriers can cause structural changes and allow foreign antigens and pathogens to bypass the first line of defense of the innate system. As they persist, S. aureus can secrete various virulence factors to enhance their survival by host invasion and evasion mechanisms. In response, epithelial cells can release damage-associated molecular patterns, or alarmins such as TSLP, IL-25, IL-33, and chemokines, to recruit innate and adaptive immune cells to cause infla...
Cells
Staphylococcus aureus superantigens (SAgs) have been reported to aggravate atopic dermatitis. However, comprehensive analyses of these molecules in multiple microniches are lacking. The present study involved 50 adult patients with active atopic dermatitis. S. aureus was isolated from the lesional skin, nonlesional skin, and anterior nares. Multiplex-PCR was performed to identify genes encoding (1) selX (core genome); (2) seg, selI, selM, selN, selO, selU (enterotoxin gene cluster, EGC); and (3) sea, seb, sec, sed, see, tstH (classic SAgs encoded on other mobile genetic elements). The results were correlated to clinical parameters of the study group. selx and EGC were the most prevalent in all microniches. The number of SAg-encoding genes correlated between the anterior nares and nonlesional skin, and between the nonlesional and lesional skin. On lesional skin, the total number of SAg genes correlated with disease severity (total and objective SCORAD, intensity, erythema, edema/papu...
British Journal of Dermatology, 2009
Background Staphylococcus aureus (S. aureus) is a well-known trigger factor of atopic dermatitis (AD). Besides staphylococcal superantigens, a-toxin may influence cutaneous inflammation via induction of T-cell proliferation and cytokine secretion. Objectives To investigate the association between sensitization to inhalant allergens and skin colonization with a-toxin-producing S. aureus in AD. Patients and methods We investigated 127 patients with AD, aged 14-65 years, who were on standard anti-inflammatory and antiseptic treatment before investigation. We evaluated skin colonization, medical history, severity of AD and sensitization to inhalant allergens. Results Forty-eight of 127 patients were colonized with S. aureus, suffered from more severe AD, had asthma more often and showed higher sensitization levels to inhalant allergens. Thirty of 48 patients with S. aureus skin-colonizing strains produced a-toxin and had higher total IgE and specific IgE to birch pollen and timothy grass pollen. Conclusions Under topical treatment with antiseptic and anti-inflammatory agents the colonization of lesional skin with S. aureus was clearly lower than commonly found in untreated patients with AD. Colonization with S. aureus was associated with a higher severity of AD, higher degree of sensitization, and a higher frequency of asthma. The proportion of patients whose skin was colonized with a-toxin-producing S. aureus was higher than expected from a former study. Cutaneous colonization with a-toxin-producing S. aureus was associated with a higher sensitization level to birch pollen allergen in AD. This may point to a higher susceptibility of patients with higher T-helper 2 polarization towards a-toxin-producing S. aureus.
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2005
Background Staphylococcus aureus is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by S. aureus and may have an influence on the eczema. Objective To explore the impact of staphylococcal a-toxin on human T cells, as those represent the majority of skin infiltrating cells in AD. Methods Adult patients with AD were screened for cutaneous colonization with a-toxin producing S. aureus. As a-toxin may induce necrosis, CD4 1 T cells were incubated with sublytic a-toxin concentrations. Proliferation and up-regulation of IFN-g on the mRNA and the protein level were assessed. The induction of t-bet translocation in CD4 1 T cells was detected with the Electrophoretic Mobility Shift Assay. Results Thirty-four percent of the patients were colonized with a-toxin producing S. aureus and a-toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic a-toxin concentrations induced a marked proliferation of isolated CD4 1 T cells. Microarray analysis indicated that a-toxin induced particularly high amounts of IFN-g transcripts. Up-regulation of IFN-g was confirmed both on the mRNA and the protein level. Stimulation of CD4 1 T cells with a-toxin resulted in DNA binding of t-bet, known as a key transcription factor involved into primary T helper type 1 (Th1) commitment. Conclusion a-toxin is produced by S. aureus isolated from patients with AD. We show here for the first time that sublytic a-toxin concentrations activate T cells in the absence of antigen-presenting cells. Our results indicate that a-toxin is relevant for the induction of a Th1 like cytokine response. In AD, this facilitates the development of Th1 cell dominated chronic eczema.
Journal of Allergy and Clinical Immunology, 2000
Background: The skin of patients with atopic dermatitis (AD) exhibits a striking susceptibility to colonization with Staphylococcus aureus. Some strains of S aureus secrete exotoxins with T-cell superantigen activity (toxigenic strains), and abnormal T-cell functions are known to play a critical role in AD. Objective: Our purpose was to examine the impact of superantigen production by skin-colonizing S aureus on disease severity.