Document Detail

Toll-like receptor 7 inhibits early acute retroviral infection through rapid lymphocyte responses.
MedLine Citation:
PMID:  23616654     Owner:  NLM     Status:  MEDLINE    
Early events during retroviral infection play a critical role in determining the course of infection and pathogenesis, but the mechanisms that regulate this phase of infection are poorly understood. Toll-like receptor 7 (TLR7) is required for promoting germinal center reactions and virus-specific neutralizing antibodies at later time points postinfection, but TLR7's role in early acute infection has not been determined. By infecting TLR7-deficient mice with a retroviral pathogen, Friend virus (FV), I determined that TLR7 potently inhibits retroviral replication during the first 5 days of infection and is required for rapid secretion of virus-specific IgM and interleukin-10 (IL-10) in response to infection. Although the IgM response was nonneutralizing, plasmas from wild-type mice but not TLR7-deficient mice inhibited FV replication when passively transferred to infected mice, suggesting an indirect mechanism of antibody function. Interestingly, IL-10 was secreted primarily by CD4 T cells, and IL-10-deficient mice also exhibited accelerated early virus spread, demonstrating that this response inhibits acute infection. Surprisingly, TLR7-deficient mice exhibited normal or elevated secretion of proinflammatory cytokines during acute infection, revealing the existence of a TLR7-independent retrovirus-sensing pathway that drives inflammatory cytokine secretion. Together, these results establish a previously unappreciated role for lymphocytes in mediating rapid TLR7-dependent inhibition of early retroviral infection through nonneutralizing IgM and IL-10.
Edward P Browne
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Publication Detail:
Type:  Journal Article     Date:  2013-04-24
Journal Detail:
Title:  Journal of virology     Volume:  87     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-11     Completed Date:  2013-08-12     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7357-66     Citation Subset:  IM    
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MeSH Terms
CD4-Positive T-Lymphocytes / immunology*
Cytokines / immunology
Flow Cytometry
Friend murine leukemia virus / immunology*
Immunoglobulin M / immunology
Interleukin-10 / immunology
Membrane Glycoproteins / genetics,  immunology*
Mice, Inbred C57BL
Retroviridae Infections / immunology*
Toll-Like Receptor 7 / genetics,  immunology*
Virus Replication / immunology
Reg. No./Substance:
0/Cytokines; 0/Immunoglobulin M; 0/Membrane Glycoproteins; 0/Tlr7 protein, mouse; 0/Toll-Like Receptor 7; 130068-27-8/Interleukin-10

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