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Pathogen evasion of PRR signaling pathway eg: HCV interact with PRRs Fig1: structure of HCV * HCV interact with PRRs * Paper Discussion （1）： Role of TLR7 in WNV infection (Town T et al., 2009 Immunity; IF20) ssRNA— dsRNA (during replication) * Fig 1: Increased Susceptibility of Tlr7?/? and Myd88?/? Mice, but Not Tlr9?/? Mice, after West Nile Virus Challenge WT: 50%死亡 TLR7-/-: 90%死亡 TLR7 ：抗病毒作用 * Fig 2. Tlr7- and Myd88-Dependent Viral Load and Innate Immune Cytokine Responses after West Nile Virus Challenge：Viral Load: ↑ Cytokine： IL23, IL12 ↓ * Fig 3：Immune Cell Homing to WNV-Infected Cells In Vivo depends on TLR7 Green： WNV （More in TLR7 -/-） Red： Immune Cells (Less in TLR6 -/-) * Immune Cell Homing Homing的意义： 1、淋巴细胞得以合理的再分布及补充； 2、增加抗原和淋巴细胞的接触机会，产生有效的免疫应答。(免疫细胞有效的迁移到受感染的部位)。 * TLR7 dependant macrophage homing Less cell infiltration * Fig 4. Macrophage Homing to West Nile Virus Is IL-23 Signaling Dependent Macrophage Virus Homing Issue Brain section staining * Summary: TLR7 mediated anti-WNV function Immune Cell Homing Virus Clearance * Paper discussion (2): Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. (Wang P. et al., Nature Immunology 2010) Caspase 12 -/- : Less survival; Severe neurological symptoms * 1) Viral load ↑↑ in Caspase 12-/- mice * 2) ↓↓INFb production in Caspase12 -/- mice * 3) Caspase12 interacts with RIG-I/TRIM25 * 4) Less Ub-RIG-I in Caspase 12-/- mice Ub- RIG-I Total RIG-I Total TRIM25 * Story Summary: Caspase12 is required for RIG-I Ub →IFNb production （Caspase 12 的抗病毒作用） C