Role of innate lymphoid cells on experimental sepsis-induced cognitive decline.

Abstract

Abstract Background Sepsis is a disordered host immune reaction to pathogen invasion that leads to organ dysfunction, high mortality, and long-term consequences. More than 50% of sepsis survivors often suffer from severe and long-term cognitive deficits. We previously demonstrated in vivo microglial activation and neuroinflammation associated with cognitive deficits in an experimental model of sepsis. Recent studies have demonstrated the role of innate lymphoid cells (ILCs) in aging and neurodegeneration-induced cognitive loss. ILCs are enriched at barrier surfaces and regulate inflammation and tissue homeostasis in a disease condition. Here we aimed to explore the role of ILCs subtypes on experimental sepsis-induced cognitive deficits. Methods Male, 50-day-old C57BL/6 mice were subjected to cecal ligation and perforation (CLP) surgery to induce sepsis or sham surgery as a control group. At 10 days after sepsis, assessment of cognition was performed using novel object recognition (NOR) task. The ILCs subtypes ILC1, ILC2, and ILC3 were evaluated in the spleen, meninges, and choroid plexus (CP) using multicolor flow cytometry. Results Sepsis groups demonstrated cognitive decline as measured by decreased recognition index as compared to the control group. In the periphery, the spleen from the sepsis group demonstrated increased ILC1 and ILC3 levels as compared to control groups. In brain barriers, we observed increased accumulation of ILC2 subtype in CP in the sepsis group. However, there was no difference in the meningeal accumulation of ILCs between control and sepsis groups. Conclusion Targeting group 2 innate lymphoid cells may provide a new strategy to combat sepsis-associated long-term cognitive deficits. Supported by Alzheimer's Association grant to TB - AARGDNTF-19-619645. NIH/NIA grant to TB - 1RF1AG072491-01.