Macrophage inflammatory protein 3alpha deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus.
BACKGROUND
Patients with atopic dermatitis (AD) are prone to disseminated viral skin infections and therefore are not vaccinated against smallpox because of potential complications. Macrophage inflammatory protein 3alpha (MIP-3alpha) is a C-C chemokine expressed by keratinocytes that exhibits antimicrobial activity against bacteria and fungi; however, its role in antiviral innate immunity is unknown.


OBJECTIVE
Evaluate the level of MIP-3alpha in AD skin and its role in the innate immune response to vaccinia virus (VV).


METHODS
Macrophage inflammatory protein 3alpha levels were evaluated using real-time RT-PCR, immunodot-blot, and immunohistochemistry. The antiviral activity of MIP-3alpha was determined using a standard viral plaque assay.


RESULTS
Macrophage inflammatory protein 3alpha gene expression was significantly (P < .01) decreased in AD skin (0.21 +/- 0.05 ng MIP-3alpha/ng glyceraldehyde-3-phosphate dehydrogenase) compared with psoriasis skin (0.67 +/- 0.13). This was confirmed at the protein level using immunohistochemistry. We further demonstrate that T(H)2 cytokines downregulate MIP-3alpha expression. The importance of MIP-3alpha in the innate immune response against VV was established by first demonstrating that MIP-3alpha exhibits activity against VV. Second, VV replication was significantly increased (P < .01) in keratinocytes treated with an antibody to neutralize MIP-3alpha.


CONCLUSIONS
The current study demonstrates that MIP-3alpha exhibits antiviral activity against VV and demonstrates the importance of MIP-3alpha in the innate immune response against VV. In addition, AD skin is deficient in MIP-3alpha, in part because of the overexpression of T(H)2 cytokines in AD skin.


CONCLUSIONS
MIP-3alpha deficiency in AD skin contributes to patients' increased propensity toward eczema vaccinatum. Increasing MIP-3alpha or neutralizing T(H)2 cytokines could prevent adverse reactions in patients with AD after smallpox vaccination.
Kim
Byung Eui
BE
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Leung
Donald Y M
DY
Streib
Joanne E
JE
Kisich
Kevin
K
Boguniewicz
Mark
M
Hamid
Qutayba A
QA
Howell
Michael D
MD
D000328:Adult; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology; D012867:Skin / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins