Severe Ocular Cowpox in a Human, Finland.
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ABSTRACT:
SUBMITTER: Kinnunen PM
PROVIDER: S-EPMC4672437 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and monocyte-derived DCs (MDDCs). A CPXV infection of DCs at a multiplicity of infection of 10 was nonproductive, altered cellular morphology, and failed to reduce cell viability. A CPXV infection of DCs did not stimulate cytokine or chemokine secretion directly, but suppressed toll-like receptor (TLR) agonist-induced cytokine secretion and a DC-stimulated mixed leukocyte reaction (MLR). LPS-stimulated NF-?B nuclear translocation and host cytokine gene transcription were suppressed in CPXV-infected MDDCs. Early viral immunomodulatory genes were upregulated in MDDCs, consistent with early DC immunosuppression via synthesis of intracellular viral proteins. We conclude that a nonproductive CPXV infection suppressed DC immune function by synthesizing early intracellular viral proteins that suppressed DC signaling pathways.
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Project description:The commensal microbiota is involved in a variety of diseases. Our group has noticed that patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) often present with persistent inflammation of the ocular surface, even in the chronic stage, and that this inflammation is exacerbated by colonization of the mucosa by certain bacteria. However, the changes in the composition of the ocular microbiome in SJS/TEN patients with severe ocular complications (SOCs) remain to be fully investigated. Here, we conducted a cross-sectional study of 46 Japanese subjects comprising 9 healthy control subjects and 37 SJS/TEN patients with SOC. The 16S rRNA-based genetic analyses revealed that the diversity of the ocular microbiome was reduced in SJS/TEN patients with SOC compared with that in healthy control subjects. Principal coordinate analysis based on Bray-Curtis distance at the genus level revealed that the relative composition of the ocular microbiome was different in healthy control subjects and SJS/TEN patients with SOC, and that the SJS/TEN patients with SOC could be divided into four groups based on whether their microbiome was characterized by enrichment of species in genus Corynebacterium 1, Neisseriaceae uncultured, or Staphylococcus or by simultaneous enrichment in species in genera Propionibacterium, Streptococcus, Fusobacterium, Lawsonella, and Serratia. Collectively, our findings indicate that enrichment of certain bacteria at the ocular surface could be associated with ocular surface inflammation in SJS/TEN patients with SOC.
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