The MAB-5/Hox family transcription factor is important for Caenorhabditis elegans innate immune response to Staphylococcus epidermidis infection

Abstract

Innate immunity functions as a rapid defense against broad classes of pathogenic agents. While the mechanisms of innate immunity in response to antigen exposure are well-studied, how pathogen exposure activates the innate immune responses and the role of genetic variation in immune activity is currently being investigated. Previously we showed significant survival differences between the N2 and CB4856 Caenorhabditis elegans isolates in response to Staphylococcus epidermidis infection. One of those differences was expression of the mab-5 Hox-family transcription factor, which was induced in N2, but not CB4856, after infection. Here we use survival assays and RNA-sequencing to better understand the role of mab-5 in response to S. epidermidis. We found that mab-5 loss-of-function mutants were more susceptible to S. epidermidis infection than N2 or mab-5 gain-of-function mutants, but not as susceptible as CB4856 animals. We then conducted transcriptome analysis of infected worms and found considerable differences in gene-expression profiles when comparing animals with mab-5 loss-of-function to either N2 or mab-5 gain-of-function. N2 and mab-5 gain-of-function animals showed a significant enrichment in expression of immune genes and C-type lectins, whereas mab-5 loss-of-function mutants did not. Overall, gene expression profiling in mab-5 mutants provided insight into MAB-5 regulation of the transcriptomic response of C. elegans to pathogenic bacteria and helps us to understand mechanisms of innate immune activation and the role that transcriptional regulation plays in organismal health.