Abstract
The investigation of the molecular background of direct communication of neurons and immune cells in the brain is an important issue for understanding physiological and pathological processes in the nervous system. Direct contacts between brain-infiltrating immune cells and neurons, and the neuromodulatory effect of immune cell-derived regulatory peptides are well established. Several aspects of the role of immune and glial cells in the direct neuro-immune communication are also well known; however, there remain many questions regarding the molecular details of signaling from neurons to immune cells. Thus, we report here on the neuronal expression of genes encoding antimicrobial and immunomodulatory peptides, as well as proteins of immune cell-specific activation and communication mechanisms. In the present study, we analyzed the single-cell sequencing data of our previous transcriptomic work, obtained from electrophysiologically identified pyramidal cells and interneurons of the murine prefrontal cortex. We filtered out the genes that may be associated with the direct communication between immune cells and neurons and examined their expression pattern in the neuronal transcriptome. The expression of some of these genes by cortical neurons has not yet been reported. The vast majority of antimicrobial (~53%) and immune cell protein (~94%) transcripts was identified in the transcriptome of the 84 cells, owing to the high sensitivity of ultra-deep sequencing. Several of the antimicrobial and immune process-related protein transcripts showed cell type-specific or enriched expression. Individual neurons transcribed only a fraction of the investigated genes with low copy numbers probably due to the bursting kinetics of gene expression; however, the comparison of our data with available transcriptomic datasets from immune cells and neurons suggests the functional relevance of the reported findings. Accordingly, we propose further experimental and in silico studies on the neuronal expression of immune system-related genes and the potential role of the encoded proteins in neuroimmunological processes.
Highlights
In the last decades, our knowledge about neuro-immune communication progressed and several complex molecular interactions between the immune system and the central nervous system (CNS) have been revealed
The raw sequencing data of the 84 prefrontal cortical (PFC) neurons contained more than 19,000 transcripts, which is comparable to the estimated number of proteins in a mammalian cell [26]
We report here on mRNAs of AMPs with immunomodulatory function and proteins involved in lymphocyte activation and antigen presentation mechanisms expressed by prefrontal Pyr and FS cells harvested after electrophysiological identification
Summary
Our knowledge about neuro-immune communication progressed and several complex molecular interactions between the immune system and the central nervous system (CNS) have been revealed. It became clear that the main processes of neuro-immune crosstalk in the brain are performed by microglial cells and astrocytes [1]. Modulatory effects of immune system-derived cytokines were described in psychiatric and mental illnesses and in the healthy brain [2, 3]. The neuronal origin of defensins was not established. Defensins are antimicrobial peptides which are part of the innate immune system and have immunomodulatory effects; besides eliminating bacteria, fungi, and viruses, b-defensins were shown to be chemotactic for T cells through C-C chemokine receptor type 6 (CCR6 receptor) [6, 7]. Expression of b-defensins and some other antimicrobial peptides has been found in microglial cells and astrocytes [8], but not in neurons
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