Cathelicidin deficiency predisposes to eczema herpeticum

J Allergy Clin Immunol. 2006 Apr;117(4):836-41. doi: 10.1016/j.jaci.2005.12.1345. Epub 2006 Feb 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Animals
  • Antimicrobial Cationic Peptides / deficiency*
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / immunology
  • Antimicrobial Cationic Peptides / pharmacology
  • Base Sequence
  • 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

Substances

  • Antimicrobial Cationic Peptides
  • DNA, Viral
  • Recombinant Proteins
  • CAP18 lipopolysaccharide-binding protein
  • Immunoglobulin E