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The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model.

Abstract：

:The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model. Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice (WT) and a panel of mouse strains lacking specific innate immunity component expression. We found higher levels of HBV protein production and replication in Tlr2-/-, Tlr23479-/-, 3d/Tlr24-/-, Myd88/Trif-/- and Irak4-/- mice, which was associated with reduced HBV-specific CD8+ T-cell responses in these mice. Importantly, HBV clearance was delayed for more than 2 weeks in 3d/Tlr24-/-, Myd88/Trif-/- and Irak4-/- mice compared to WT mice. HBV-specific CD8+ T-cell responses were functionally impaired for producing the cytokines IFN-γ, TNF-α and IL-2 in TLR signaling-deficient mice compared to WT mice. In conclusion, the IL-1R/TLR signaling pathway might contribute to controlling HBV infection by augmenting HBV-specific CD8+ T-cell responses.

journal_name

Cell Mol Immunol

journal_title

Cellular & molecular immunology

authors

Ma Z,Liu J,Wu W,Zhang E,Zhang X,Li Q,Zelinskyy G,Buer J,Dittmer U,Kirschning CJ,Lu M

doi

10.1038/cmi.2017.43

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

997-1008

issue

12

eissn

1672-7681

issn

2042-0226

pii

cmi201743

journal_volume

14

pub_type

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