Macrophage inflammatory protein 3α 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 3α (MIP-3α) 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-3α in AD skin and its role in the innate immune response to vaccinia virus (VV). Methods Macrophage inflammatory protein 3α levels were evaluated using real-time RT-PCR, immunodot-blot, and immunohistochemistry. The antiviral activity of MIP-3α was determined using a standard viral plaque assay. Results Macrophage inflammatory protein 3α gene expression was significantly ( P < .01) decreased in AD skin (0.21 ± 0.05 ng MIP-3α/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 TH 2 cytokines downregulate MIP-3α expression. The importance of MIP-3α in the innate immune response against VV was established by first demonstrating that MIP-3α exhibits activity against VV. Second, VV replication was significantly increased ( P < .01) in keratinocytes treated with an antibody to neutralize MIP-3α. Conclusion The current study demonstrates that MIP-3α exhibits antiviral activity against VV and demonstrates the importance of MIP-3α in the innate immune response against VV. In addition, AD skin is deficient in MIP-3α, in part because of the overexpression of TH 2 cytokines in AD skin. Clinical implications MIP-3α deficiency in AD skin contributes to patients' increased propensity toward eczema vaccinatum. Increasing MIP-3α or neutralizing TH 2 cytokines could prevent adverse reactions in patients with AD after smallpox vaccination.