Toll-like receptor 7 is not necessary for retroviral neuropathogenesis but does contribute to virus-induced neuroinflammation.
Toll-like receptor 7 (TLR7) recognizes guanidine-rich single-stranded (ss) viral RNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs is not as clear. This is particularly true in the central nervous system (CNS) where microglia and astrocytes are often the first cells responding to virus infection instead of dendritic cells. In the current study, we examined the mechanism by which TLR7 contributes to ssRNA virus-induced neuroinflammation using a mouse model of polytropic retrovirus infection. The authors found that TLR7 was necessary for the early production of certain cytokines and chemokines, including CCL2 and tumor necrosis factor (TNF) and was also involved in the early activation of astrocytes. However, TLR7 was not necessary for cytokine production and astrocyte activation at later stages of infection and did not alter viral pathogenesis or viral replication in the brain. This suggests that other pathogen recognition receptors may be able to compensate for the lack of TLR7 during retrovirus infection in the CNS.
Lewis
Stephanie D
SD
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Butchi
Niranjan B
NB
Khaleduzzaman
Mohammed
M
Morgan
Tim W
TW
Du
Min
M
Pourciau
Susan
S
Baker
David G
DG
Akira
Shizuo
S
Peterson
Karin E
KE
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000276:immunology* / Q000821:virology; D001921:Brain / Q000821:virology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D016899:Interferon-beta / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012190:Retroviridae / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D014779:Virus Replication
D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta