Although there were bunch of results showing the defined role of dendritic cells (DCs) in initiating adaptive host defense, their potential contributions to T-cell independent innate host defense and to subsequent immunopathology in immune privileged central nervous system (CNS) by neurotrophic virus is not completely defined. Notably, the potential roles of DC-monocyte interaction during neuroinflammatory course have not yet been addressed in depth. Here we found that CD11c^highPDCA-1^int/low DCs are essential to control the progression of neuroinflammation in immune privileged CNS upon infection of neurotrophic Japanese encephalitis virus (JEV), using selective ablation of CD11c^highPDCA-1^int/low DCs without altered CD11c^intPDCA-1^high plasmacytoid DC number, as manifested by increased CD11b⁺Ly-6C^high monocyte infiltration, blood-brain barrier (BBB) permeability, viral burden, and cytokine expression. More surprisingly, CD11b⁺Ly-6C^high monocytes were observed to have deleterious role in viral encephalitis, and selective ablation of CD11c^highPDCA-1^int/low DCs provided altered differentiation and function of infiltrated CD11b⁺Ly-6C^high monocytes in CNS. Subsequently, CD11b⁺Ly-6C^high monocytes generated in the absence of CD11c^highPDCA-1^int/low DCs elicited faster recruitment into inflamed CNS depending on CCR2, and augmented the severity of neuroinflammation caused by JEV infection, as were proved by several experimental models including adoptive transfer of CD11b⁺Ly-6C^high monocytes using CCR2 KO and CCR2 KOCD11c-DTR BM chimera. Our data identify for the first time an unrecognized role of CD11c^highPDCA-1^int/low DCs in maintaining the functional homeostasis of inflammatory CD11b⁺Ly-6C^high monocytes and integrity of BBB, thereby affecting immunopathology in immune privileged CNS by neurotrophic virus