Time of day alters olfactory bulb immune state with ramifications for intranasal inflammatory challenge

The circadian and immune systems are important for tissue homeostasis, yet their integration in the brain remains understudied. The olfactory bulb, a brain region that exhibits robust circadian rhythms and is regularly exposed to inflammatory stimuli, provides an optimal locus to probe the interaction of these two systems. We find that the murine olfactory bulb rhythmically expresses immune-related transcripts, with antiviral transcripts peaking around dusk. This is accompanied by distinct transcriptional responses to intranasal poly(I:C) (a virus-like immune stimulus) at dusk versus dawn, suggesting that time of day primes the olfactory bulb's response to inflammatory challenges. Using imaging and spectral flow cytometry, we detect and characterize distinct subpopulations of microglia, the resident macrophages of the brain, which differentially respond to intranasal poly(I:C) depending on time of day. This unveils a clear relationship between time of day and olfactory bulb immune processes, suggesting time is an important dimension to consider when studying the olfactory pathway into the brain.