title: Microglia-induced IL-6 protects against neuronal loss following HSV-1 infection of neural progenitor cells.
abstract: Herpes virus type 1 (HSV-1) is one of the most widespread human pathogens and accounts for more than 90% of cases of herpes simplex encephalitis (HSE) causing severe and permanent neurologic sequelae among surviving patients. We hypothesize such CNS deficits are due to HSV-1 infection of neural progenitor cells (NPCs). In vivo, HSV-1 infection was found to diminish NPC numbers in the subventricular zone. Upon culture of NPCs in conditions that stimulate their differentiation, we found HSV-1 infection of NPCs resulted in the loss of neuronal precursors with no significant change in the percentage of astrocytes or oligodendrocytes. We propose this is due a direct effect of HSV-1 on neuronal survival without alteration of the differentiation process. The neuronal loss was prevented by the addition of microglia or conditioned media from NPC/microglia co-cultures. Using neutralizing antibodies and recombinant cytokines, we identified interleukin-6 (IL-6) as responsible for the protective effect by microglia, likely through its downstream Signal Transducer and Activator of Transcription 3 (STAT3) cascade.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Chucair-Elliott
authors.forename: Christopher
authors.initials: C
authors.lastname: Conrady
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Chandra M
authors.initials: CM
authors.lastname: Kroll
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lane
authors.forename: Daniel J J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006561:Herpes Simplex / Q000473:pathology / Q000503:physiopathology*; D018259:Herpesvirus 1, Human; D015850:Interleukin-6 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000473:pathology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014709:Vero Cells
chemical_list: D015850:Interleukin-6; C577485:Nes protein, mouse; D064231:Nestin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D049452:Green Fluorescent Proteins
keywords: cytokines; encephalitis; protection; stem cells; virus