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IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection
- Source :
- European Journal of Immunology. 43:1529-1544
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- Dengue virus (DENV), a mosquito-borne flavivirus, is a public health problem in many tropical countries. IL-22 and IL-17A are key cytokines in several infectious and inflammatory diseases. We have assessed the contribution of IL-22 and IL-17A in the pathogenesis of experimental dengue infection using a mouse-adapted DENV serotype 2 strain (P23085) that causes a disease that resembles severe dengue in humans. We show that IL-22 and IL-17A are produced upon DENV-2 infection in immune-competent mice. Infected IL-22(-/-) mice had increased lethality, neutrophil accumulation and pro-inflammatory cytokines in tissues, notably IL-17A. Viral load was increased in spleen and liver of infected IL-22(-/-) mice. There was also more severe liver injury, as seen by increased transaminases levels and tissue histopathology. γδ T cells and NK cells are sources of IL-17A and IL-22, respectively, in liver and spleen. We also show that DENV-infected HepG2 cells treated with rhIL-22 had reduced cell death and decreased IL-6 production. IL-17RA(-/-) mice were protected upon infection and IL-17A-neutralizing-Ab-treatment partially reversed the phenotype observed in IL-22(-/-) -infected mice. We suggest that disrupting the balance between IL-22 and IL-17A levels may represent an important strategy to reduce inflammation and tissue injury associated with severe dengue infection.
- Subjects :
- Liver injury
0303 health sciences
biology
Immunology
Spleen
Inflammation
Dengue virus
medicine.disease
medicine.disease_cause
biology.organism_classification
Virology
3. Good health
Dengue fever
Interleukin 22
Pathogenesis
03 medical and health sciences
Flavivirus
0302 clinical medicine
medicine.anatomical_structure
medicine
Immunology and Allergy
medicine.symptom
030304 developmental biology
030215 immunology
Subjects
Details
- ISSN :
- 00142980
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi...........be6205d645ef6bff605d5e4e7e15e082