Abstract
Ebola virus causes an acute hemorrhagic fever lethal in primates and rodents. The contribution of host immune factors to pathogenesis has yet to be determined and may reveal efficacious targets for potential treatment. In this study, we show that the interleukin (IL)-10 signaling pathway modulates Ebola pathogenesis. IL-10(-/-) mice and wild-type mice receiving antisense targeting IL-10 signaling via disrupting expression through aberrant splice altering were resistant to ebola virus infection. IL-10(-/-) mice exhibited reduced viral titers, pathology, and levels of IL-2, IL-6, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-1 α and increased interferon (IFN)-γ relative to infected wild-type mice. Furthermore, antibody depletion studies in IL-10(-/-) mice suggest a requirement for natural killer cells and IFN-γ for protection. Together, these data demonstrate that resistance to ebola infection is regulated by IL-10 and can be targeted in a prophylactic manner to protect against lethal hemorrhagic virus challenge.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alternative Splicing
-
Animals
-
Antibodies, Viral / biosynthesis*
-
Antiviral Agents / chemical synthesis
-
Antiviral Agents / immunology*
-
Chemokine CCL3 / genetics
-
Chemokine CCL3 / immunology
-
Chemokines / genetics
-
Chemokines / immunology
-
Disease Susceptibility
-
Drug Discovery
-
Ebolavirus / immunology*
-
Female
-
Gene Expression Regulation
-
Hemorrhagic Fever, Ebola / genetics*
-
Hemorrhagic Fever, Ebola / immunology
-
Hemorrhagic Fever, Ebola / mortality
-
Hemorrhagic Fever, Ebola / therapy
-
Host-Pathogen Interactions
-
Immunity, Innate
-
Interferon-gamma / genetics
-
Interferon-gamma / immunology
-
Interleukin-10 / antagonists & inhibitors
-
Interleukin-10 / deficiency
-
Interleukin-10 / genetics
-
Interleukin-10 / immunology*
-
Interleukin-2 / genetics
-
Interleukin-2 / immunology
-
Interleukin-6 / genetics
-
Interleukin-6 / immunology
-
Killer Cells, Natural / immunology*
-
Mice
-
Mice, Inbred C57BL
-
RNA, Small Interfering / chemical synthesis
-
RNA, Small Interfering / genetics*
-
RNA, Small Interfering / immunology
-
Signal Transduction
Substances
-
Antibodies, Viral
-
Antiviral Agents
-
Ccl3 protein, mouse
-
Chemokine CCL3
-
Chemokines
-
IL10 protein, mouse
-
Interleukin-2
-
Interleukin-6
-
RNA, Small Interfering
-
Interleukin-10
-
keratinocyte-derived chemokines
-
Interferon-gamma