Specificity and Complexity of the Caenorhabditis elegans Innate Immune Response

Abstract

In response to infection, Caenorhabditis elegans produces an array of antimicrobial proteins. To understand the C. elegans immune response, we have investigated the regulation of a large, representative sample of candidate antimicrobial genes. We found that all these putative antimicrobial genes are expressed in tissues exposed to the environment, a position from which they can ward off infection. Using RNA interference to inhibit the function of immune signaling pathways in C. elegans, we found that different immune response pathways regulate expression of distinct but overlapping sets of antimicrobial genes. We also show that different bacterial pathogens regulate distinct but overlapping sets of antimicrobial genes. The patterns of genes induced by pathogens do not coincide with any single immune signaling pathway. Thus, even in this simple model system for innate immunity, striking specificity and complexity exist in the immune response. The unique patterns of antimicrobial gene expression observed when C. elegans is exposed to different pathogens or when different immune signaling pathways are perturbed suggest that a large set of yet to be identified pathogen recognition receptors (PRRs) exist in the nematode. These PRRs must interact in a complicated fashion to induce a unique set of antimicrobial genes. We also propose the existence of an "antimicrobial fingerprint," which will aid in assigning newly identified C. elegans innate immunity genes to known immune signaling pathways.

Antimicrobial effectors in the nematode Caenorhabditis elegans : an outgroup to the Arthropoda

“…In C. elegans, this is most likely the case for those effectors which we here show to be inducible by non-pathogenic microbes (e.g. lys-4, ilys-3 and spp-18; figure 3), and also those which are constitutively expressed, as previously shown for spp-5 [49], abf-1, abf-2 and abf-3 [63,71,74]. As suggested for spp-5 [49], constitutively expressed effector genes might function in both defence and digestion, because they could enable the worm to access bacteria-derived nutrients and at the same time eliminate potential pathogens.…”

“…The expression of several lysozyme genes was shown to be controlled by C. elegans immune signalling pathways. For example, lys-7 and lys-8 are known targets of DAF-16 (FOXO) [62] and the TGF-b pathway [70,71]. Expression of lys-2 is regulated by the GATA transcription factor ELT-2 and the p38 MAPK PMK-1 [72].…”

Role for a somatically diversified lectin in resistance of an invertebrate to parasite infection

“…FREP3 up-regulation is also associated with heightened responsiveness following priming with attenuated digenetic trematodes (acquired resistance) in this model invertebrate immune system. (1), worms (2), snails (3), flies (4), sea urchins (5), and lampreys (6). One of the insights emerging from these studies is that invertebrates, although they do not have adaptive immune systems in the sense of those possessed by jawed vertebrates, nonetheless do have sophisticated innate immune systems that have revealed an unforeseen ability to produce diversified antigen recognition molecules (3,4).…”

Comparative Genomics RNAi Screen Identifies Eftud2 as a Novel Regulator of Innate Immunity

“…In response to infection, C. elegans produces numerous antimicrobial proteins including lysozymes, saposin-domain-containing proteins, defensin-like molecules, and many others (Ewbank 2006;Ewbank and Zugasti 2011). Production of these antimicrobials occurs in tissues exposed to pathogens and is regulated by conserved innate immune signaling pathways, including a p38 MAPK cascade, an insulin signaling pathway, a TGFb cascade, and others (Mochii et al 1999;Mallo et al 2002;Murphy et al 2003;Couillault et al 2004;Huffman et al 2004;O'Rourke et al 2006;Shapira et al 2006;Troemel et al 2006;Alper et al 2007). Inhibition or mutation of genes in these conserved signaling pathways diminishes production of antimicrobial genes and enhances susceptibility to infection.…”