Immune Netw.  2007 Jun;7(2):66-74. 10.4110/in.2007.7.2.66.

Flaviviruses Induce Pro-inflammatory and Anti-inflammatory Cytokines from Murine Dendritic Cells through MyD88-dependent Pathway

• Aleyas AG
• George JA
• Han YW
• Kim HK
• Kim SJ
• Yoon HA
• Eo SK

• KMID: 2150628
• DOI: http://doi.org/10.4110/in.2007.7.2.66

Abstract

BACKGROUND: The genus Flavivirus consists of many emerging arboviruses, including Dengue virus (DV), Japanese encephalitis virus (JEV) and West Nile virus (WNV). Effective preventive vaccines remain elusive for these diseases. Mice are being increasingly used as the animal model for vaccine studies. However, the pathogenic mechanisms of these viruses are not clearly understood. Here, we investigated the interaction of DV and JEV with murine bone marrow-derived dendritic cells (bmDC).
METHODS
ELISA and FACS analysis were employed to investigate cytokine production and phenotypic changes of DCs obtained from bone marrow following flavivirus infection.
RESULTS
We observed that these viruses altered the cytokine profile and phenotypic markers. Although both viruses belong to the same family, JEV-infected bmDC produced anti-inflammatory cytokine (IL-10) along with pro-inflammatory cytokines, whereas DV infection induced production of large amounts of pro-inflammatory cytokines (IL-6 and TNF-alpha) and no IL-10 from murine bmDCs. Both flaviviruses also up-regulated the expression of co-stimulatory molecules such as CD40, CD80 and CD86. JEV infection led to down-regulation of MHC II expression on infected bmDCs. We also found that cytokine production induced by JEV and DV is MyD88-dependent. This dependence was complete for DV, as cytokine production was completely abolished in the absence of MyD88. With regard to JEV, the absence of MyD88 led to a partial reduction in cytokine levels.
CONCLUSION
Here, we demonstrate that MyD88 plays an important role in the pathogenesis of flaviviruses. Our study provides insight into the pathogenesis of JEV and DV in the murine model.

Keyword

Japanese encephalitis virus (JEV); Dengue virus (DV); bone marrow-derived dendritic cells (bmDCs); IL-10; IL-6; TNF-alpha; MyD88

MeSH Terms

Animals
Arboviruses
Bone Marrow
Cytokines*
Dendritic Cells*
Dengue Virus
Down-Regulation
Encephalitis Virus, Japanese
Enzyme-Linked Immunosorbent Assay
Flavivirus Infections
Flavivirus*
Humans
Interleukin-10
Interleukin-6
Mice
Models, Animal
Tumor Necrosis Factor-alpha
Vaccines
West Nile virus
Cytokines
Interleukin-10
Interleukin-6
Tumor Necrosis Factor-alpha
Vaccines