Monocytes maintain central nervous system homeostasis following helminth-induced inflammation

Abstract

Neuroimmune interactions are crucial for regulating immunity and inflammation. Recent studies have revealed that the central nervous system (CNS) senses peripheral inflammation and responds by releasing molecules that limit immune cell activation, thereby promoting tolerance and tissue integrity. However, the extent to which this is a bidirectional process, and whether peripheral immune cells also promote tolerance mechanisms in the CNS remains poorly defined. Here we report that helminth-induced type 2 inflammation promotes monocyte responses in the brain that are required to inhibit excessive microglial activation and host death. Mechanistically, infection-induced monocytes express YM1 that is sufficient to inhibit tumor necrosis factor production from activated microglia. Importantly, neuroprotective monocytes persist in the brain, and infected mice are protected from subsequent lipopolysaccharide-induced neuroinflammation months after infection-induced inflammation has resolved. These studies demonstrate that infiltrating monocytes promote CNS homeostasis in response to inflammation in the periphery and demonstrate that a peripheral infection can alter the immunologic landscape of the host brain.

Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome

“…By integrating estimated cell-type compositions, our analysis revealed that the post-infusion DEG signature was primarily driven by changes in monocyte-specific gene expression. Monocytes, as immune cells involved in inflammatory responses, play crucial roles in shaping the immune milieu within the central nervous system (Peng, et al, 2022; Arteaga-Henríquez, et al, 2022; Xie, et al, 2017). The upregulation of genes associated with immune and inflammatory processes observed in our study aligns with previous evidence highlighting the involvement of the immune system in the pathophysiology of neurodevelopmental disorders, including ASD (Arteaga-Henríquez, et al, 2022l; Molloy, et al, 2005; Gupta, et al, 1998; Dantzer, et al, 2008).…”

Targeting helminths: The expanding world of type 2 immune effector mechanisms

“…Neuroprotection also occurs during the intestinal response to Trichinella spiralis , where monocytes recruited to the brain express M2 markers and inhibit excessive microglial cell activation. This tolerance mechanism persists for months and also protects against lipopolysaccharide-induced neuroinflammation ( Peng et al, 2022 ).…”