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Effector-triggered immunity (ETI) enables hosts to react to pathogens by monitoring few key cellular processes. ETI responses are assumed to be similar toward related pathogen effectors. However, recent evidence from the invertebrate model Caenorhabditis elegans and pore-forming toxins indicates a much more complex and specific ETI than previously anticipated. [ABSTRACT FROM AUTHOR]

Invertebrate defence against pathogens exclusively relies on components of the innate immune system. Comprehensive information has been collected over the last years on the molecular components of invertebrate immunity and the involved signalling processes, especially for the main invertebrate model species, the fruitfly Drosophila melanogaster and the nematode Caenorhabditis elegans . Yet, the exact regulation of general and specific defences is still not well understood. In the current study, we take advantage of a recently established database, WormExp, which combines all available gene expression studies for C. elegans , in order to explore commonalities and differences in the regulation of nematode immune defence against a large variety of pathogens versus food microbes. We identified significant overlaps in the transcriptional response towards microbes, especially pathogenic bacteria. We also found that the GATA motif is overrepresented in many microbe-induced gene sets and in targets of other previously identified regulators of worm immunity. Moreover, the activated targets of one of the known C. elegans GATA transcription factors, ELT-2, are significantly enriched in the gene sets, which are differentially regulated by gut-infecting pathogens. These findings strongly suggest that GATA transcription factors and particularly ELT-2 play a central role in regulating the C. elegans immune response against gut pathogens. More specific responses to distinct pathogens may be mediated by additional transcription factors, either acting alone or jointly with GATA transcription factors. Taken together, our analysis of the worm's transcriptional response to microbes provides a new perspective on the C. elegans immune system, which we propose to be coordinated by GATA transcription factor ELT-2 in the gut. [ABSTRACT FROM AUTHOR]

Pathogen infection can activate multiple signaling cascades that ultimately alter the abundance of molecules in cells. This change can be measured both at the transcript and protein level. Studies analyzing the immune response at both levels are, however, rare. Here, we compare transcriptome and proteome data generated after infection of the nematode and model organism Caenorhabditis elegans with the Gram-positive pathogen Bacillus thuringiensis . Our analysis revealed a high overlap between abundance changes of corresponding transcripts and gene products, especially for genes encoding C-type lectin domain-containing proteins, indicating their particular role in worm immunity. We additionally identified a unique signature at the proteome level, suggesting that the C. elegans response to infection is shaped by changes beyond transcription. Such effects appear to be influenced by AMP-activated protein kinases (AMPKs), which may thus represent previously unknown regulators of C. elegans immune defense. [ABSTRACT FROM AUTHOR]

C-type lectin-like domain (CTLD) proteins occupy crucial functions in the immune system of vertebrates, but their role in invertebrate immunity is much less understood. The nematode Caenorhabditis elegans possesses a highly diverse CTLD protein encoding ( clec ) gene repertoire. A role of C. elegans clec genes in pathogen defense is always assumed, yet experimental evidence for clec immune function is rare. To systematically test the potential function of clec genes in the C. elegans defense against pathogens, we screened 39 clec mutants for survival on the Gram-positive pathogen Bacillus thuringiensis (BT18247) and 37 clec mutants on the Gram-negative pathogen Pseudomonas aeruginosa (PA14). We found that clec mutants can exhibit either decreased or, unexpectedly, increased resistance to infection. Since we observed high escape behavior for some of the clec mutants on BT18247 during the initial screen, we then asked if increased pathogen avoidance behavior underlies the increased resistance of some clec mutants. We thus tested lawn leaving behavior of the resistant clec-29(ok3181) , clec-34(ok2120) , clec-151(ok2264) , and C54G4.4(ok2110) mutant on BT18247. We found that C54G4.4(ok2110) mutant animals exhibit a particularly strong lawn leaving behavior, in addition to prolonged feeding cessation when exposed to BT18247. Together, our results indicate that clec genes mediate both resistance and susceptibility to infection. Further, behavioral analyses of the C54G4.4(ok2110) mutant implicate C54G4.4 in the regulation of pathogen avoidance behavior towards BT18247. We conclude that C. elegans clec genes may act both as positive and negative regulators of physiological as well as behavioral immune defense responses. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are small non-coding RNA-molecules that influence translation by binding to the target gene mRNA. Many miRNAs are found in nested arrangements within larger protein-coding host genes. miRNAs and host genes in a nested arrangement are often transcribed simultaneously, which may indicate that both have similar functions. miRNAs have been implicated in regulating defense responses against pathogen infection in C. elegans and in mammals. Here, we asked if miRNAs in nested arrangements and their host genes are involved in the C. elegans response against infection with Bacillus thuringiensis (Bt). We performed miRNA sequencing and subsequently focused on four nested miRNA-host gene arrangements for a functional genetic analysis. We identified mir-58.1 and mir-2 as negative regulators of C. elegans resistance to Bt infection. However, we did not find any miRNA/host gene pair in which both contribute to defense against Bt. [Display omitted] • 12% of C. elegans miRNA genes are significantly differentially expressed after B. thuringiensis (Bt) infection. • 50% of downregulated miRNAs are nested within a similarly downregulated host gene. • Loss of mir-58.1 and mir-2 leads to enhanced resistance to Bt. • Loss of the miRNA host genes ppfr-1 and pmp-5 leads to susceptibility to Bt. • miRNAs and their host genes likely act independently in nematode defense against Bt. [ABSTRACT FROM AUTHOR]