<i>Staphylococcus aureus</i> and Hyper-IgE Syndrome
Hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections, eczema, skeletal abnormalities and high titers of serum immunoglobulin E. Although the genetic basis of HIES was...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/23/9152 |
| Summary: | Hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections, eczema, skeletal abnormalities and high titers of serum immunoglobulin E. Although the genetic basis of HIES was not known for almost a half century, HIES most frequently exhibits autosomal dominant trait that is transmitted with variable expressivity. Careful genetic studies in recent years identified dominant-negative mutations in human signal transducer and activator of transcription 3 (<i>STAT3</i>) gene as the cause of sporadic and dominant forms of HIES. The <i>STAT3</i> mutations were localized to DNA-binding, SRC homology 2 (SH2) and transactivating domains and disrupted T helper 17 (T<sub>H</sub>17) cell differentiation and downstream expression of T<sub>H</sub>17 cytokines IL-17 and IL-22. Deficiency of IL-17 and IL-22 in turn is responsible for suboptimal expression of anti-staphylococcal host factors, such as neutrophil-recruiting chemokines and antimicrobial peptides, by human keratinocytes and bronchial epithelial cells. T<sub>H</sub>17 cytokines deficiency thereby explains the recurrent staphylococcal lung and skin infections of HIES patients. |
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| ISSN: | 1661-6596 1422-0067 |