UC Santa Cruz

Circadian rhythms regulate changes in physiology and allow organisms to respond to predictable environmental demands over 24 hours. Recent studies have shown that the circadian system is an essential regulator of immune function. Additionally, disruption of the circadian clock affects our immune response. However, how bacterial infection affects our circadian clock, which affects our immune response, remains unclear. Here, we found that the addition of heat-killed S. pneumoniae (HK Spn) to mouse lung fibroblast cells impacts their circadian rhythms through acute induction of clock protein PER2. Due to the acute induction of PER2, it resets the cells to a different phase. Moreover, HK Spn can affect the PER2 rhythm throughout the clock, and interestingly, HK Spn resets the clock of these mouse lung fibroblasts to the same circadian time. Furthermore, we also identify the dose-dependent effect of HK Spn on PER2 rhythm. Gram-positive bacteria and gram-negative bacteria are evolutionarily different from each other. Nonetheless, we find that all tested bacteria trigger the same PER2 response. Therefore, this response is an evolutionarily conserved response within all bacteria. Furthermore, we identify that TLR2 and TLR4 are not responsible for this bacterially induced PER2 induction. My work also focuses on the downstream of the signaling pathway, where we characterize that the PER2 response is post-transcriptional and likely mTOR-independent. Together, our results advance understanding of the bidirectionality effect between circadian rhythms and bacterial infections.