Vaccinia virus–specific molecular signature in atopic dermatitis skin

Grigoryev, Dmitry N.; Howell, Michael D.; Watkins, Tonya; Chen, Shen‐Ming; Cheadle, Chris; Boguniewicz, Mark; Barnes, Kathleen C.; Leung, Donald Y.M.

doi:10.1016/j.jaci.2009.10.024

Cited by 27 publications

(30 citation statements)

References 37 publications

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“…Direct studies of VV infection in in vitro or mouse models have also helped to elucidate the mechanisms of VV infection in AD. The studies by Bin et al [74] and Grigoryev et al [75] provide further insight on the genes that are critical for the innate immune responses against VV. These in turn may lead to novel approaches in treating or preventing VV infection in AD e.g.…”

Section: Discussionmentioning

confidence: 99%

“…These findings were seen in both European and African Americans [74]. More recently, microarray analyses were applied to study VV-induced transcriptional changes in unaffected skin explants obtained from AD, psoriatic, and healthy individuals [75]. The skin samples were treated in vitro with vehicle or VV and subjected to gene ontology analysis.…”

Section: The Role Of Viral Skin Infections In Admentioning

confidence: 99%

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The Infectious Aspects of Atopic Dermatitis

Ong

Leung

2010

Immunology and Allergy Clinics of North America

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SynopsisAtopic dermatitis is characterized by S. aureus colonization and recurrent skin infections. In addition to an increased risk of invasive infections by herpes simplex or vaccinia viruses, there is ample evidence that microbial pathogens, particularly S. aureus and fungi, contribute to the cutaneous inflammation of atopic dermatitis. We describe recent developments in the pathogenesis of atopic dermatitis in relation to the role of microbial pathogens. Understanding how microbial pathogens interact or evade the cutaneous immunity of atopic dermatitis may be crucial in preventing infections or cutaneous inflammation in this disease.

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Section: Discussionmentioning

confidence: 99%

Section: The Role Of Viral Skin Infections In Admentioning

confidence: 99%

The Infectious Aspects of Atopic Dermatitis

Ong

Leung

2010

Immunology and Allergy Clinics of North America

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“…IFN-γ receptor knockout mice that received VV vaccine by scarification developed disseminated VV skin lesions, significant weight loss, and reduced survival, as compared to control mice [64]. Ex vivo studies using human skin explants for microarray analyses of AD, psoriasis, and healthy subjects suggest the importance of innate immunity genes in VV infection [70]. These genes include leukotriene B4 receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and lipopolysaccharide binding protein (LBP), all of which were found to be significantly downregulated in VV-treated AD explants, as compared to that of healthy individuals or psoriasis patients.…”

Section: The Role Of Viral Skin Infections In Admentioning

confidence: 99%

Bacterial and Viral Infections in Atopic Dermatitis: a Comprehensive Review

Ong

Leung

2016

Clinic Rev Allerg Immunol

217

197

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Atopic dermatitis (AD) is the most common allergic skin disease in the general population. It is a chronic inflammatory skin disease complicated by recurrent bacterial and viral infections that, when left untreated, can lead to significant complications. The current article will review immunologic and molecular mechanisms underlying the propensity of AD patients to microbial infections. These infections include Staphylococcus aureus (S. aureus) skin infections, eczema herpeticum, eczema vaccinatum, and eczema coxsackium. Previous studies have shown that skin barrier defects, a decrease in antimicrobial peptides, increased skin pH, or Th2 cytokines such as IL-4 and IL-13 are potential contributing factors for the increased risk of skin infections in AD. In addition, bacterial virulence such as methicillin-resistant S. aureus (MRSA) produces significantly higher number of superantigens that increase their potential in causing infection and more severe cutaneous inflammation in AD patients. More recent studies suggest that skin microbiome including Staphylococcus epidermidis or other coagulase-negative staphylococci may play an important role in controlling S. aureus skin infections in AD. Other studies also suggest that genetic variants in the innate immune response may predispose AD patients to increased risk of viral skin infections. These genetic variants include thymic stromal lymphopoietin (TSLP), type I interferon (α, ß, ω), type II interferon (γ), and molecular pathways that lead to the production of interferons (interferon regulatory factor 2). A common staphylococcal toxin, α-toxin, may also play a role in enhancing herpes simplex virus skin infections in AD. Further understanding of these disease processes may have important clinical implications for the prevention and treatment of skin infections in this common skin disease.

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“…A large percentage of the current U.S. population have conditions that contraindicate receipt of the vaccine (immunosuppression due to: cancer, organ transplants, HIV infection, heart conditions, and skin diseases such as eczema or psoriasis)(Fenner 1989). Altered cytokine responses to vaccinia inoculation in individuals with atopic dermatis are believed to be responsible for the higher incidence of eczema vaccinatum (Grigoryev et al 2010; Howell et al 2006; Scott et al 2007). Furthermore, Th2 responses are correlated with impaired viral clearance,(Freyschmidt et al 2007) while animal models where expression of key cytokines are intentionally over- or under-expressed clearly indicate that cytokine production in response to poxvirus infection or inoculation can greatly influence the course of the viral infection (Foong et al 2009; Kohyama et al 2007; Sharma et al 1996; Tian et al 2009; van Den Broek et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients

et al. 2012

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The role that genetics plays in response to infection or disease is becoming increasingly clear as we learn more about immunogenetics and host-pathogen interactions. Here we report a genome-wide analysis of the effects of host genetic variation on cytokine responses to vaccinia virus stimulation in smallpox vaccine recipients. Our data show that vaccinia stimulation of immune individuals results in secretion of inflammatory and Th1 cytokines. We identified multiple SNPs significantly associated with variations in cytokine secretion. These SNPs are found in genes with known immune function, as well as in genes encoding for proteins involved in signal transduction, cytoskeleton, membrane channels and ion transport, as well as others with no previously identified connection to immune responses. The large number of significant SNP associations implies that cytokine secretion in response to vaccinia virus is a complex process controlled by multiple genes and gene families. Follow-up studies to replicate these findings and then pursue mechanistic studies will provide a greater understanding of how genetic variation influences vaccine responses.

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Vaccinia virus–specific molecular signature in atopic dermatitis skin

Cited by 27 publications

References 37 publications

The Infectious Aspects of Atopic Dermatitis

The Infectious Aspects of Atopic Dermatitis

Bacterial and Viral Infections in Atopic Dermatitis: a Comprehensive Review

Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients

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