Introduction Microglia are heterogenous mononuclear phagocytic immune cells of the central nervous system (CNS) and their functions aim to maintain brain homeostasis. CNS immune plasticity permits either immune training or tolerance against previously challenged pathogenic stimuli, which serves to exacerbate or repress the neuroinflammatory response, respectively. Here, it is hypothesised that microglia are required for executing CNS immune memory. To test this, the Csf1rΔFIRE/ΔFIRE transgenic mouse model was assessed for the presence of CNS immune memory. This model contains a deletion of an intronic enhancer sequence of the colony stimulating factor 1 receptor (Csf1r) gene and are absent of microglia from birth. MethodsC57BL/6J and Csf1rΔFIRE/ΔFIRE mice received an intraperitoneal injection of liposaccharide (LPS) as a single challenge (1x) or once every 24 hours over 4 consecutive days (4x). 3 hours post final injection mice were sacrificed. Brains were assessed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) for transcriptional profiling. Hippocampal and microglial images were collected after immunohistochemistry. Approach for statistical analysisMice were grouped according to their respective treatment and confirmed genotype. Image and gene expression analyses were performed using One Way ANOVA/ Post-Hoc Tukey test. Significance was defined by p<0.05. Results and ConclusionsIn C57BL6/J mice, a single challenge of LPS induced CNS neuroinflammation through transcriptionally up-regulating pro-inflammatory factors. However, the transcriptional induction of these pro-inflammatory factors was significantly weaker after 4x LPS treatment. This is indicative of CNS immune tolerance following subsequent LPS challenges, and thereby supports the presence of immune memory. Transcriptional upregulation of microglial associated markers was likewise detected after 4x LPS treatment. Moreover, the Csf1rΔFIRE/ΔFIRE model was identically treated and the transcriptional responses of these inflammatory and microglial markers will be measured. This will identify whether CNS immune tolerance to systemic LPS is consistent in the absence of microglia. Taken together, the Csf1rΔFIRE/ΔFIRE model will provide further insight into the participation of microglia in the process of CNS immune tolerance.
|Publication status||Published - 12 Apr 2021|
|Event||British Neuroscience Association 2021 : Festival of Neuroscience - Virtual|
Duration: 12 Apr 2021 → 15 Apr 2021
|Conference||British Neuroscience Association 2021|
|Period||12/04/21 → 15/04/21|
- Innate immune memory