Dendritic cell immunoreceptor regulates Chikungunya virus pathogenesis in mice
Autor(es): Long Kristin M, Whitmore Alan C, Ferris Martin T, Sempowski Gregory D, McGee Charles, Trollinger Bianca, Gunn Bronwyn, Heise Mark T
Resumo: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for recent epidemic outbreaks of debilitating disease in humans. Alphaviruses are known to interact with members of the C-type lectin receptor family of pattern recognition proteins, - given that the dendritic cell immunoreceptor (DCIR) is known to act as a negative regulator of the host inflammatory response - has previously been associated with rheumatoid arthritis, we evaluated DCIR's role in response to CHIKV infection. Although we observed an increase in the proportion of dendritic cells at the site of CHIKV infection at 24 to 36 h postinfection, these cells showed decreased cell surface DCIR, suggestive of DCIR triggering - internalization. In vitro, bone marrow-derived dendritic cells from DCIR-deficient (DCIR(-/-)) mice exhibited altered cytokine expression following exposure to CHIKV. DCIR(-/-) mice exhibited more severe disease signs than wild-type C57BL6/J mice following CHIKV infection, including a more rapid - more severe onset of virus-induced edema - enhanced weight loss. Histological examination revealed that DCIR-deficient animals exhibited increased inflammation - damage in both the fascia of the inoculated foot - the ankle joint, - DCIR deficiency skewed the CHIKV-induced cytokine response at the site of infection at multiple times postinfection. Early differences in virus-induced disease between C57BL6/J - DCIR(-/-) mice were independent of viral replication, while extended viral replication correlated with enhanced foot swelling - tissue inflammation - damage in DCIR(-/-) compared to C57BL6/J mice at 6 to 7 days postinfection. These results suggest that DCIR plays a protective role in limiting the CHIKV-induced inflammatory response - subsequent tissue - joint damage.
Imprenta: Journal of Virology, v. 87, n. 10, p. 5697-5706, 2013
Identificador do objeto digital: 10.1128/JVI.01611-12
Descritores: Chikungunya virus - Biochemistry ; Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology
Data de publicação: 2013
