Role Of Infiltrating Macrophage In Neuroinflammation Following Infection And Obesity In Mice

Obesity, inflammation and infections are linked to increased cognitive impairment, anxiety and dementia in later life. Previous data from our lab demonstrate a diet high in saturated fat, leading to obesity, prolongs inflammation in the brains of latently herpes simplex virus (HSV)‐infected mice and results in increases in anxiety behaviors. In this study, we sought to determine the contribution of infiltrating monocytes/macrophage to the prolonged neuroinflammation in the obese, latently infected mice. C57Bl/6 and CCR2RFP/+/CX3CR1GFP/+ mice, which allow for the differentiation of microglia from infiltrating mononuclear cells, were used in this study. Weanling mice were placed on the low fat diet. Five days post weaning, the mice were infected with a low dose of herpes simplex (HSV)‐1. After 14 days half of the mice were moved to the 45% lard/soybean oil diet. At various points following infection, we determined the number and phenotype of infiltrating cells using immunohistochemistry, flow cytometry and FACS sorting. We found that in latently infected mice on the HF diet there was greater infiltration of macrophage and increased microglial activation compared to LF mice. The infiltrating macrophage also produced proinflammatory cytokines demonstrating that along with activated microglia, infiltrating macrophage contribute to neuroinflammation in latently infected obese mice.