Dynamics of an innate myeloid cell response to acute CNS viral infection

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NINDS	NEURO/BEHAV/SENSYS-23

* FARE Award Winner

Authors

• D Nayak
• S Heydari
• B Zinselmeyer
• K Johnson
• D McGavern

Abstract

Viral infections of central nervous system (CNS) often trigger an inflammatory response with varied pathological consequences. The CNS is equipped with an elaborate network of innate immune sentinels that routinely serve as first responders to these infections. The meninges and perivascular spaces are inhabited by specialized macrophages, and the brain parenchyma contains microglia – the most abundant CNS myeloid cell. To gain novel insights into how myeloid cells respond to an acute viral infection, we utilized genomics and two-photon imaging approaches to study a pure innate response to LCMV infection. This was accomplished by monitoring temporal gene expression patterns and myeloid cell dynamics in the brains of CX3CR1-GFP mice lacking LCMV-specific T cells. Two-photon imaging studies revealed that microglia responded significantly by sequestering DsRed-labeled virus. Microglia but not peripheral myeloid cells proliferated following acute infection and responded directly to viral antigen by reducing process complexity, suggesting a localized response to the presence of virus. However, acute infection triggered massive changes in CNS gene expression with the majority of genes being linked to innate viral control and the type-I interferon system. These data suggest that localized virus detection by CNS myeloid sentinels can translate into engagement of an extensive anti-viral program.

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