Regulation of the Intracellular Pathogen Response by pals Gene Pairs in C. elegans
The innate immune system is critical in protecting against foreign invaders and can be activated by detection of microbe-associated molecules, as well as detection of the consequences of pathogen infection. In the nematode C. elegans, the molecularly diverse intracellular pathogens of microsporidia and virus can induce a common host transcriptional response called the Intracellular Pathogen Response (IPR). The IPR can also be induced by proteotoxic stress, which is often a consequence of intracellular infection. In parallel, the IPR is regulated by antagonistic paralogs in C. elegans called pals-22 and pals-25. The wild-type function of pals-22 is to repress IPR gene expression and increase thermotolerance and pathogen resistance, while the wild-type function of pals-25 is to activate these phenotypes, acting downstream of pals-22. To investigate how pals genes control the IPR, I further characterized the role of pals-22/pals-25, as well as two additional pals pairs: pals-17/pals-20 and pals-23/pals-24. First, I investigated the role of pals-22 and pals-25 in mediating the induction of IPR genes upon proteotoxic stress. Next, I characterized pals-17 as another negative regulator of IPR genes and found that pals-17 may work with an antagonistic paralog pals-20 as an activator. Finally, I knocked out another pals gene pair, pals-23 and pals-24, and found that they do not regulate expression of a GFP reporter for the IPR gene pals-5. Altogether, these findings demonstrate general principles of host gene regulation by antagonistic paralogs, which control expression of genes that promote resistance against natural intracellular pathogens and tolerance of proteotoxic stress.