Microglial response to viral challenges: Every silver lining comes with a cloud

Microglia, the resident macrophages of the Central Nervous System (CNS) mediate key innate immune responses against foreign invasions within the CNS and clear the debris after any damage to the nearby tissue. Blood Brain Barrier (BBB) segregates the CNS from the rest of the lymphatic system and prevents the entry of foreign molecules into the brain. Pathogens still cross the BBB via different mechanisms and can cause severe infections of the CNS. Viral encephalitis is the most common form of brain infection and the causative agents include Japanese Encephalitis Virus (JEV), West Nile Virus (WNV), Murray Valley Encephalitis Virus (MVEV), Herpes Simplex Virus (HSV), Human Immunodeficiency Virus (HIV), Cytomegalovirus (CMV) and Hepatitis C Virus (HCV) among several others. Microglia expresses various Pattern Recognition Receptors (PRRs) to identify viral signatures called Pathogen Associated Molecular Patterns (PAMPs) to which microglia respond by releasing several pro and anti-inflammatory cytokines like MCP1, IL-1beta, Type I IFN, IFN-gamma, TNF-alpha etc. This review discusses the various viral infections of the brain and strategies employed by microglia to detect them.