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Aging and reduced exposure to environmental microbes can both potentiate neuroinflammatory responses. Prior studies indicate that immunization with the immunoregulatory and anti-inflammatory bacterium,  Mycobacterium vaccae  ( M. vaccae ), in aged rats limits neuroimmune activation and cognitive impairments. However, the mechanisms by which  M. vaccae  immunization ameliorates age-associated neuroinflammatory “priming” and whether microglia are a primary target remain unclear. Here, we investigated whether  M. vaccae  immunization protects against microglia morphological changes in response to aging. Adult (3 mos) and aged (24 mos) Fisher 344 × Brown Norway rats were immunized with either  M. vaccae  or vehicle once every week for 3 weeks. Aging led to elevated Iba1 immunoreactivity, microglial density, and deramification of microglia processes in the hippocampus and amygdala but not other brain regions. Additionally, aged rats exhibited larger microglial somas in the dorsal hippocampus, suggestive of a more activated phenotype. Notably,  M. vaccae  treatment ameliorated indicators of microglia activation in both the amygdala and hippocampus. While changes in morphology appeared to be region-specific, gene markers indicative of microglia activation were upregulated by age and lowered in response to  M. vaccae  in all brain regions evaluated. Taken together, these data suggest that peripheral immunization with  M. vaccae  quells markers of age-associated microglia activation.

Mycobacterium vaccae immunization in rats ameliorates features of age-associated microglia activation in the amygdala and hippocampus