NK cell-mediated destruction of influenza A virus-infected peripheral but not central neurones.
Peripheral neurones have the potential to transmit infectious agents to the central nervous system (CNS). This raises the possibility of existing host defence mechanisms that may prevent such spread. Natural killer (NK) cells can target infected cells, and by this ability serve to limit spread of infection prior to the development of adaptive immune responses. To address directly if NK cells can target infected peripheral neurones, we examined the expression of NK cell-activating ligands and susceptibility to NK cell-mediated cytolytic effects in ex vivo cultures of mouse peripheral dorsal root ganglia (DRG) neurones prior to and after infection with a neurotropic strain of influenza A virus, WSN/33. In infected DRG cultures, retinoic acid early inducible gene-1 (RAE-1) transcripts were induced and exposure to interleukin (IL)-2-activated NK cells resulted in a total destruction of neurites. Studies on cultures from interferon (IFN)-alpha/betaR-deficient mice suggest that the infection engages an IFN-alpha/beta-dependent signalling pathway to induce RAE-1 transcripts. In contrast, induction of RAE-1 transcripts or NK cell-mediated neurite destructions was not observed in central hippocampal neurones. This reveals distinct properties between peripheral DRG and central hippocampal neurones with respect to the ability to signal for immune destruction following infection.
Backström
E
E
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. ebackstrom@bccrc.ca
Ljunggren
H-G
HG
Kristensson
K
K
D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005727:Ganglia, Spinal / Q000276:immunology / Q000821:virology*; D006624:Hippocampus / Q000276:immunology / Q000821:virology*; D007150:Immunohistochemistry; D009980:Influenza A virus / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000821:virology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000635:transmission; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism
D016898:Interferon-alpha; C502844:Rai1 protein, mouse; D015534:Trans-Activators; D016899:Interferon-beta