Transcriptome Profiling Across Multiple Organs Unveils Potential Roles of C-Fibers in Host Homeostatic Regulation in Mice

Abstract

Abstract As nociceptors, C-fibers play a critical role in maintaining host homeostasis under both physiological and pathological conditions. We previously demonstrated that C-fiber degeneration confers protection against respiratory syncytial virus (RSV) infection. However, a comprehensive investigation on the effects of C-fiber degeneration on the physiological state of the host remains unexplored. To address this gap, we established a C-fiber-degenerated (KCF) BALB/c mouse model and validated it by immunofluorescence staining of multiple organs. We monitored the body weight of KCF mice and performed 16S rRNA sequencing of their feces. And their brains, lungs, intestines, and spleen were subjected to section staining and RNA sequencing. Although no significant changes in body weight or tissue pathology were observed, KCF mice showed significant tran-scriptional alterations in four examined organs. The lungs and intestines exhibited diminished proportions of resting mast cells, while the spleens displayed reduced proportions of monocytes. Functional enrichment analysis revealed the involvement of C-fibers in the production of immunoglobulin and changes in intestinal microbiota. Subsequent experiments confirmed a trend towards reduced globulin levels in the peripheral blood and marked alterations in the diversity and composition of intestinal microbiota. Integrated analysis of differentially expressed genes shared by all four organs identified the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway as a pivotal route by which C-fibers may influence these organs. In summary, this study elucidates the diverse regulatory roles that C-fibers play in maintaining host homeostasis, extending our understanding in a multi-organ context.