IFNAR signaling of olfactory sensory neurons is dispensable for the control of viral entry into the CNS via the olfactory route

Identification: Chhatbar, Chintan


Description

 

IFNAR signaling of olfactory sensory neurons is dispensable for the control of viral entry into the CNS via the olfactory route
 
Chintan Chhatbar1, Luca Ghita1, Andreas Pavlou2, Claudia N. Detje1, Martin Stangel2,3, and Ulrich Kalinke1
1Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany; 2Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany; 3Center for Systems Neuroscience, Hannover, Germany
Contact: ulrich.kalinke@twincore.de
 
Previous experiments indicated that upon intranasal VSV instillation olfactory sensory neurons are infected and the virus moves along their axons into the olfactory bulb. There, astrocytes and to a lesser extent neurons are activated to express IFN-beta. Interestingly, IFNAR triggering of neurons is needed in order to confer full microglia activation, as indicated by impaired accumulation and activation of Iba-1+ CNS-resident myeloid cells in the olfactory bulb of mice which lack IFNAR signaling on neurons. To address whether IFNAR signaling of olfactory sensory neurons was also needed to activate microglia upon VSV entry via the olfactory route, here we studied OMP-cre+/-IFNARfl/fl mice showing a selective IFNAR deletion on olfactory sensory neurons. Interestingly, upon intranasal VSV instillation these mice controlled the virus as efficiently as cre negative littermate controls with intact IFNAR signaling. Currently, we are studying microglia activation and accumulation within the olfactory bulb of these animals. Our preliminary data indicate that in OMP-cre+/-IFNARfl/fl mice microglia activation and accumulation within OB is normal. These data suggest that not the IFNAR signaling of olfactory sensory neurons but of other neurons or astrocytes within the olfactory bulb is critically required for microglia activation and protection against viral encephalitis.
 
Funding
This study was supported by a bilateral project of the German Centre for Neurodegenerative Diseases and the Helmholtz Centre for Infection Research (to M.S., and U.K.), by the Helmholtz “Zukunftsthema Immunology & Inflammation”, and by the Niedersachsen-Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony, Germany (to M.S. and U.K.).
 

 

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