Abstract
GATA transcription factors play critical roles in cellular differentiation and development. However, their roles in mature tissues are less understood. In C. elegans larvae, the transcription factor ELT-2 regulates terminal differentiation of the intestine. It is also expressed in the adult intestine, where it was suggested to maintain intestinal structure and function, and where it was additionally shown to contribute to infection resistance. To study the function of elt-2 in adults we characterized elt-2-dependent gene expression following its knock-down specifically in adults. Microarray analysis identified two ELT-2-regulated gene subsets: one, enriched for hydrolytic enzymes, pointed at regulation of constitutive digestive functions as a dominant role of adult elt-2; the second was enriched for immune genes that are induced in response to Pseudomonas aeruginosa infection. Focusing on the latter, we used genetic analyses coupled to survival assays and quantitative RT-PCR to interrogate the mechanism(s) through which elt-2 contributes to immunity. We show that elt-2 controls p38-dependent gene induction, cooperating with two p38-activated transcription factors, ATF-7 and SKN-1. This demonstrates a mechanism through which the constitutively nuclear elt-2 can impact induced responses, and play a dominant role in C. elegans immunity.
Highlights
Induction of local innate immune responses is the first reaction to an invading pathogen, and includes increased expression of antimicrobial effector peptides/proteins, as well as immune modulators
To identify genes regulated by elt-2, we compared gene expression profiles in animals fed with elt-2 RNAi during the first two days of adulthood (RNAi-ad) to those in control-treated animals, either following a twelve hour infection with Pseudomonas aeruginosa, or exposure to non-pathogenic E. coli
Adult elt-2 knock-down has been shown to cause a marked decrease in ELT-2 protein levels persisting up to three days after worms were removed from RNAi plates [22]
Summary
Induction of local innate immune responses is the first reaction to an invading pathogen, and includes increased expression of antimicrobial effector peptides/proteins, as well as immune modulators. Regulation of these responses depends on signaling modules that are similar in their principles of action from plants to animals, suggesting convergent evolution [1]. Within the animal kingdom these signaling modules often use similar proteins, such as pattern recognition receptors, their downstream signaling cascades, and MAP kinase signaling pathways [2,3] This conservation warrants the study of innate immune mechanisms in well-characterized invertebrate model organisms, such as Drosophila melanogaster and Caenorhabditis elegans, to better understand their vertebrate counterparts. ELT-3 was identified as a regulator of epidermal anti-fungal responses, a subset of which was regulated by the p38 pathway [16]
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