Title | IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Tian T, Jin MQiushuang, Dubin K, King SL, Hoetzenecker W, Murphy GF, Chen CAmy, Kupper TS, Fuhlbrigge RC |
Journal | J Immunol |
Volume | 198 |
Issue | 11 |
Pagination | 4341-4351 |
Date Published | 2017 06 01 |
ISSN | 1550-6606 |
Keywords | Administration, Cutaneous, Animals, CD8-Positive T-Lymphocytes, Interleukin 1 Receptor Antagonist Protein, Kaposi Varicelliform Eruption, Mice, Mice, Inbred C57BL, Mice, Knockout, Skin, Skin Diseases, Infectious, Vaccination, Vaccinia, Vaccinia virus, Virus Replication |
Abstract | The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1R1 knockout mice (IL-1R1) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than did wild-type mice. The phenotype of infected IL-1R1 mice was similar to eczema vaccinatum, a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis. Interestingly, the impaired cutaneous response of IL-1R1 mice did not reflect a systemic immune deficiency, because immunized IL-1R1 mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of wild-type mice, whereas lack of IL-1R1 permitted extension of VACV infection into dermal layers of the skin. We explored the etiology of this discrepancy and determined that IL-1R1 mice contained significantly more macrophages and monocyte-derived dendritic cells in the dermis after VACV scarification. These cells were vulnerable to VACV infection and may augment the transmission of virus to adjacent skin, thus leading to larger skin lesions and satellite lesions in IL-1R1 mice. These results suggest new therapeutic strategies for treatment of eczema vaccinatum and inform assessment of risks in patients receiving IL-1 blocking Abs for treatment of chronic inflammatory disorders. |
DOI | 10.4049/jimmunol.1500106 |
Alternate Journal | J. Immunol. |
PubMed ID | 28468973 |
PubMed Central ID | PMC5506850 |
Grant List | HHSN266200400030C / AI / NIAID NIH HHS / United States P30 AR042689 / AR / NIAMS NIH HHS / United States R01 AI097128 / AI / NIAID NIH HHS / United States |
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