Postdoctoral Fellow Boston Children's Hosp., Harvard Med. Sch. Boston, Massachusetts, United States
Disclosure(s):
Bristy Sabikunnahar, PhD: No financial relationships to disclose
Introduction/Rationale: Growing evidence suggests that peripheral infections contribute to neurodegenerative disease progression and cognitive impairment, yet the underlying neuro-immune mechanisms remain poorly understood.
Methods: Here, we used a mouse model of Influenza A virus (H1N1) respiratory infection to investigate immune responses in the central nervous system (CNS).
Results: At day 6 post-infection, we observed significant increases in microglia, perivascular macrophages, monocytes, NK cells, and neutrophils, indicating infection-driven immune activation within the CNS. Strikingly, eosinophils persisted in both brain/leptomeninges and dura mater up to 7 weeks post-infection. No viral RNA was detected in the brain at any time point, whereas lung tissue harbored high viral loads, suggesting peripheral infection as the driver of neuroinflammation. Cytokine and chemokine profiling revealed persistent elevation of CCL11 in serum at both day 6 and week 7. CCL11 has been implicated in other peripheral infection related neuroinflammation, potentially contributing to myelin loss and impaired neurogenesis, although mechanisms remain unknown. To address the role of CCL11 in CNS inflammation and dysfunction in this context, we have begun characterizing CCL11 knockout (KO) mice following influenza infection. Preliminary results indicate that CCL11-KO mice are more susceptible to infection compared to controls, highlighting a complex role for CCL11 in balancing antiviral defense and neuroinflammation. Furthermore, scRNA-seq analysis of healthy mice revealed high CCL11 expression in dural sinus smooth muscle cells, leptomeningeal fibroblasts and brain pericytes suggesting that brain border cells may contribute to local regulation of immune responses after infection.
Conclusion: Moving forward, our goal is to investigate CCL11 as a potential mediator linking peripheral respiratory infection to persistent neuroinflammation, providing insight into mechanisms by which infections may contribute to long-term brain dysfunction.
