IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection.

TitleIL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection.
Publication TypeJournal Article
Year of Publication2017
AuthorsTian T, Jin MQiushuang, Dubin K, King SL, Hoetzenecker W, Murphy GF, Chen CAmy, Kupper TS, Fuhlbrigge RC
JournalJ Immunol
Volume198
Issue11
Pagination4341-4351
Date Published2017 06 01
ISSN1550-6606
KeywordsAdministration, 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.

DOI10.4049/jimmunol.1500106
Alternate JournalJ. Immunol.
PubMed ID28468973
PubMed Central IDPMC5506850
Grant ListHHSN266200400030C / 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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