Quantitative proteomics identifies ferritin in the innate immune response ofC. elegans

Abstract

When encountering a pathogen, all organisms evoke a protective response by inducing defense mechanisms to help fight off the invader. The invertebrate model organism Caenorhabditis elegans has proven to be valuable for studies of the host response and the small nematode mounts a substantial transcriptional response to numerous pathogens. Here, we use global quantitative proteomics to profile the response to infection with E. coli strain LF82 isolated from patients suffering from Crohn's disease, an inflammatory bowel disease. We show that LF82 infection induces more than one hundred proteins. The response share many functional categories with other innate immunity studies in C. elegans, but also identifies novel host immune effector proteins. We demonstrate functional relevance for four LF82 induced proteins, including a lysozyme and a C-type lectin. The ferritin homolog FTN-2 was shown to be necessary for the full protective response against the Gram-negative LF82 and the Gram-positive pathogen Staphylococcus aureus. This study is the first to demonstrate a role for ferritin in the innate immune response of C. elegans, and our results suggests that quantitative proteomics is an attractive approach for identifying additional components in the complex immune response of the nematode.

Quantitative proteome analysis of Caenorhabditis elegans upon exposure to nematicidal Bacillus thuringiensis

“…Pseudomonas aeruginosa) [27]. At the protein level, a similar response was observed for Clec-63 and Clec-65 following incubation with pathogenic E. coli LF82 [36]. The gene of Clec-41, the protein of which was also found in higher abundance here, has been previously described to be transcriptionally induced as a reaction against P. aeruginosa [27].…”

“…In both cases, the effect of the pathogenic bacteria and the non-pathogenic Escherichia coli (OP50) on the host was studied independently. In another study, the interaction of C. elegans with the pathogenic E. coli strain LF82 in comparison to the E. coli food source strain OP50 was investigated using 14 N/ 15 N-metabolic labeling followed by GeLC-MS [36]. In the two biological situations, 117 proteins were identified at differential abundances.…”

Innate Host Defense Requires TFEB-Mediated Transcription of Cytoprotective and Antimicrobial Genes

“…3C-D) including genes that encode proteins with proposed or demonstrated antimicrobial activity, such as lysozymes, C-type lectins, antimicrobial peptides, and ferritin (Boehnisch et al, 2011; Hoeckendorf et al, 2012; Schulenburg et al, 2008; Simonsen et al, 2011; Tarr, 2012). We verified hlh-30- dependent induction of 14 genes in this group (Fig.…”

High Innate Immune Specificity through Diversified C-Type Lectin-Like Domain Proteins in Invertebrates

“…In some studies, survival analysis was combined with the generation of transgenic C. elegans strains carrying a transcriptional clec gene reporter and the subsequent analysis of spatial as well as infection-induced expression patterns in vivo [51][52][53] . These studies demonstrated that most of the investigated clec genes are expressed in the intestine ( fig.…”