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Microglia‐induced IL‐6 protects against neuronal loss following HSV‐1 infection of neural progenitor cells
Author(s) -
ChucairElliott Ana J.,
Conrady Christopher,
Zheng Min,
Kroll Chandra M.,
Lane Thomas E.,
Carr Daniel J. J.
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22689
Subject(s) - microglia , biology , herpes simplex virus , progenitor cell , stat protein , neural stem cell , immunology , in vivo , stat3 , subventricular zone , encephalitis , neuroscience , microbiology and biotechnology , virology , stem cell , inflammation , virus , signal transduction
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. GLIA 2014;62:1418–1434