The RNA-binding protein Fragile X messenger ribonucleoprotein modulates innate immune gene expression in macrophages 2250

Abstract Description Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by environmental and genetic factors impacting brain development. In addition to differences in cognition and behavior, ASD includes comorbidities such as GI tract abnormalities, allergies, and infection susceptibility linking ASD to the peripheral immune system. Fragile X messenger ribonucleoprotein (FMRP) is an RNA binding protein shown to regulate RNA processes in the developing brain. Loss of FMRP through gene silencing is the greatest genetic cause of ASD. Consistent with associations between ASD and immunity, individuals lacking FMRP are more susceptible to infections of the skin and mucosa, however, the contribution of FMRP to innate immunity remains unknown. Because macrophages act as a primary line of defense in barrier tissues, we hypothesized that FMRP also modulates critical pools of innate immune transcripts in macrophages. Immunofluorescence microscopy of macrophages demonstrated FMRP translocation from the cytoplasm to the nucleus upon infection with Listeria monocytogenes. Using RNA-seq, we identified differential gene expression of innate immune transcripts in macrophages lacking FMRP. RTqPCR revealed that macrophages lacking FMRP had impaired induction of Il6 gene expression upon infection with L. monocytogenes. Further exploring FMRP in innate immune transcript regulation will improve our understanding of how an immune response is induced. Funding Sources Supported by TNPRC start up funds; 5T32OD011083-10; TAMU CVM Trainee Research Grant; TAMU CVM Core Facility Grant. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)