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In Vitro Analysis of Myd88-mediated Cellular Immune Response to West Nile Virus Mutant Strain Infection
Published on: November 27, 2014
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TLR signaling controls lethal encephalitis in WNV-infected brain
Amir H Sabouri1, Maria Cecilia Garibaldi Marcondes2, Claudia Flynn1
1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, United States.
Brain Research
|June 15, 2014
Summary
Toll-like receptor (TLR) signaling protects against West Nile virus (WNV) encephalitis. Absence of TLR adapter molecules MyD88 and TRIF increased susceptibility and central nervous system pathology during early WNV infection.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Innate Immunity
Background:
- Toll-like receptors (TLRs) are crucial in innate immunity and activated during CNS viral infections.
- Previous work suggested excessive TLR activation correlates with pathogenic outcomes in SIV encephalitis.
- The role of TLRs in the early stages of West Nile virus (WNV) encephalitis requires further elucidation.
Purpose of the Study:
- To investigate the impact of TLR-mediated pathways on the early pathogenesis of CNS viral infections.
- To evaluate the role of MyD88 and TRIF adapter molecules in West Nile virus (WNV) infection.
Main Methods:
- Utilized a mouse model of sublethal West Nile virus (WNV) infection.
- Employed knockout mice lacking both MyD88 and TRIF adapter molecules (MyD88/Trif-/-).
- Compared WNV infection course, viral burden, cytokine expression, and CNS pathology in knockout and wild-type (WT) mice.
Main Results:
- MyD88/Trif-/- mice exhibited increased susceptibility to WNV infection by day 2 post-infection (pi).
- Impaired innate immune cytokine production was observed in knockout mice compared to WT.
- By day 6 pi, knockout mice showed higher viral burden, robust inflammatory cytokine expression, increased CNS cell infiltration, microglia activation, astrogliosis, and inflammatory trafficking.
Conclusions:
- TLR signaling pathways play a protective role in preventing lethal encephalitis during the early stages of West Nile virus infection.
- The absence of key TLR adapter molecules, MyD88 and TRIF, exacerbates WNV pathogenesis in the CNS.
- These findings highlight the critical role of TLRs in controlling viral encephalitis.
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