Cathelicidin deficiency predisposes to eczema herpeticum
Michael D Howell, Andreas Wollenberg, Richard L Gallo, Michael Flaig, Joanne E Streib, Cathy Wong, Tatjana Pavicic, Mark Boguniewicz, Donald Y M Leung, Michael D Howell, Andreas Wollenberg, Richard L Gallo, Michael Flaig, Joanne E Streib, Cathy Wong, Tatjana Pavicic, Mark Boguniewicz, Donald Y M Leung
Abstract
Background: The cathelicidin family of antimicrobial peptides is an integral component of the innate immune response that exhibits activity against bacterial, fungal, and viral pathogens. Eczema herpeticum (ADEH) develops in a subset of patients with atopic dermatitis (AD) because of disseminated infection with herpes simplex virus (HSV).
Objective: This study investigated the potential role of cathelicidins in host susceptibility to HSV infection.
Methods: Glycoprotein D was measured by means of real-time RT-PCR as a marker of HSV replication in skin biopsy specimens and human keratinocyte cultures. Cathelicidin expression was evaluated in skin biopsy specimens from patients with AD (n = 10) without a history of HSV skin infection and from patients with ADEH (n = 10).
Results: The cathelicidin peptide LL-37 (human cathelicidin) exhibited activity against HSV in an antiviral assay, with significant killing (P < .001) within the physiologic range. The importance of cathelicidins in antiviral skin host defense was confirmed by the observation of higher levels of HSV-2 replication in cathelicidin-deficient (Cnlp-/-) mouse skin (2.6 +/- 0.5 pg HSV/pg GAPDH, P < .05) compared with that seen in skin from their wild-type counterparts (0.9 +/- 0.3). Skin from patients with ADEH exhibited significantly (P < .05) lower levels of cathelicidin protein expression than skin from patients with AD. We also found a significant inverse correlation between cathelicidin expression and serum IgE levels (r2 = 0.46, P < .05) in patients with AD and patients with ADEH.
Conclusion: This study demonstrates that the cathelicidin peptide LL-37 possesses antiviral activity against HSV and demonstrates the importance of variable skin expression of cathelicidins in controlling susceptibility to ADEH. Additionally, serum IgE levels might be a surrogate marker for innate immune function and serve as a biomarker for which patients with AD are susceptible to ADEH.
Clinical implications: A deficiency of LL-37 might render patients with AD susceptible to ADEH. Therefore increasing production of skin LL-37 might prevent herpes infection in patients with AD.
Figures
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![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2727734/bin/nihms98459f1a.jpg)
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Essential role of cathelicidins in…
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Essential role of cathelicidins in controlling HSV replication in the skin. Skin biopsies…
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Expression of cathelicidin elevated in…
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Expression of cathelicidin elevated in AD as compared to ADEH skin. A .…
Figure 4
Expression of cathelicidin elevated in…
Figure 4
Expression of cathelicidin elevated in AD as compared to ADEH skin. A .…
Figure 5
Correlation between serum IgE levels…
Figure 5
Correlation between serum IgE levels and cathelicidin expression in AD and ADEH patients.…
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- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Adult
- Animals
- Antimicrobial Cationic Peptides / deficiency*
- Antimicrobial Cationic Peptides / genetics
- Antimicrobial Cationic Peptides / immunology
- Antimicrobial Cationic Peptides / pharmacology
- Base Sequence
- Cathelicidins
- DNA, Viral / genetics
- Dermatitis, Atopic / complications
- Dermatitis, Atopic / immunology
- Herpesvirus 2, Human / drug effects
- Herpesvirus 2, Human / genetics
- Herpesvirus 2, Human / pathogenicity
- Herpesvirus 2, Human / physiology
- Humans
- Immunity, Innate
- Immunoglobulin E / blood
- Kaposi Varicelliform Eruption / etiology*
- Kaposi Varicelliform Eruption / immunology
- Kaposi Varicelliform Eruption / pathology
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Recombinant Proteins / pharmacology
- Virus Replication / drug effects
- Antimicrobial Cationic Peptides
- DNA, Viral
- Recombinant Proteins
- Immunoglobulin E
- Cathelicidins
- T32 AI007365/AI/NIAID NIH HHS/United States
- R37 AI052453/AI/NIAID NIH HHS/United States
- R01 AR041256/AR/NIAMS NIH HHS/United States
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- N01AI40030/AI/NIAID NIH HHS/United States
- AR45676/AR/NIAMS NIH HHS/United States
- N01 AI040029/AI/NIAID NIH HHS/United States
- M01 RR000051/RR/NCRR NIH HHS/United States
- R01 AR041256-17/AR/NIAMS NIH HHS/United States
- AI052453/AI/NIAID NIH HHS/United States
- M01 RR000051-360942/RR/NCRR NIH HHS/United States
- U01 AI147462/AI/NIAID NIH HHS/United States
- T32 AI 07365/AI/NIAID NIH HHS/United States
- 5R21AR051634/AR/NIAMS NIH HHS/United States
- M01 RR00051/RR/NCRR NIH HHS/United States
- R21 AR051634/AR/NIAMS NIH HHS/United States
- R21 AR051634-02/AR/NIAMS NIH HHS/United States
- R01 AR045676/AR/NIAMS NIH HHS/United States
- R01 AI052453/AI/NIAID NIH HHS/United States
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![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2727734/bin/nihms98459f3.jpg)
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Expression of cathelicidin elevated in…
Figure 4
Expression of cathelicidin elevated in AD as compared to ADEH skin. A .…
Figure 4
Expression of cathelicidin elevated in…
Figure 4
Expression of cathelicidin elevated in AD as compared to ADEH skin. A .…
Figure 5
Correlation between serum IgE levels…
Figure 5
Correlation between serum IgE levels and cathelicidin expression in AD and ADEH patients.…
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2727734/bin/nihms98459f4.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2727734/bin/nihms98459f4a.jpg)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2727734/bin/nihms98459f5.jpg)
Source: PubMed