Nocardia farcinica is an opportunistic pathogen that causes nocardiosis primarily in patients with compromised immune systems. In this study, we used the genetically tractable organism Caenorhabditis elegans as a model to study the innate immune responses to N. farcinica infection. We found that unlike other pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus, N. farcinica failed to kill adult worms. In another words, adult worms exposed to N. farcinica exhibited a normal lifespan, compared with those fed the standard laboratory food bacterium Escherichia coli OP50. Interestingly, deletion of three core genes (pmk-1, nsy-1 and sek-1) in the p38 MAPK/PMK-1 pathway reduced the survival of worm exposure to N. farcinica, highlighting a crucial role of this pathway for C. elegans in resistance to N. farcinica. Furthermore, our results revealed that N. farcinica exposure up-regulated the level of PMK-1 phosphorylation. The activation of PMK-1 promoted nuclear translocation of a transcription factor SKN-1/Nrf2, which in turn mediated N. farcinica infection resistance in C. elegans. Our results provide an excellent example that the integrity of immune system is key aspect for counteract with pathogenesis of N. farcinica.
Keywords: C. elegans; Nocardia farcinica; SKN-1; immune integrity; p38 MAPK signaling.