Caenorhabditis elegans, a Model Organism for Investigating Immunity

Abstract

The nematode Caenorhabditis elegans has been a powerful experimental organism for almost half a century. Over the past 10 years, researchers have begun to exploit the power of C. elegans to investigate the biology of a number of human pathogens. This work has uncovered mechanisms of host immunity and pathogen virulence that are analogous to those involved during pathogenesis in humans or other animal hosts, as well as novel immunity mechanisms which appear to be unique to the worm. More recently, these investigations have uncovered details of the natural pathogens of C. elegans, including the description of a novel intracellular microsporidian parasite as well as new nodaviruses, the first identification of viral infections of this nematode. In this review, we consider the application of C. elegans to human infectious disease research, as well as consider the nematode response to these natural pathogens.

A Stenotrophomonas maltophilia Strain Evades a Major Caenorhabditis elegans Defense Pathway

“…7B). These results support a role for lys-1 and the upstream pathways that regulate lys-1 in the C. elegans defense response to JCMS, while DAF-2/16-de- (20,40), S. maltophilia JCMS accumulates in the gut and causes intestinal distention. In contrast to P. aeruginosa (58) and/or B. thuringiensis (24), JCMS virulence requires the presence of proliferating bacteria and does not involve a toxin.…”

“…Conversely, the functions of other innate immune pathways are conserved and studying the nematode immune response can be informative in understanding how higher organisms mount pathogen defenses (18,19). For example, the highly conserved p38 mitogen-activated protein kinase (MAPK) pathway plays a major role in the response to human bacterial pathogens (20) such as Pseudomonas aeruginosa (21) and Staphylococcus aureus (22). The unfolded-protein response (UPR) ire-1-xbp-1 module is a downstream target of the p38 MAPK pathway in response to pore-forming toxin (PFT) (23), a virulence factor for a number of bacterial pathogens, including Bacillus thuringiensis (24).…”

“…Each of the conserved innate immune pathways specifically regulates downstream effectors such as lysozymes, lectins, neuropeptide-like peptides (NLPs), and antimicrobial factors (reviewed in reference 20). For example, dbl-1 regulates caenacins but not the structurally related NLPs (25).…”

Zinc Cluster Transcription Factors Alter Virulence in Candida albicans

“…C. elegans is a useful model to study infectious disease. A rich body of literature demonstrates that molecular mechanisms of infectious disease progression in C. elegans are mechanistically similar to humans ( Pukkila-Worley et al 2009, 2011; also reviewed in Engelmann and Pujol 2010;Marsh and May 2012). We identified seven mutants, CMP1, IFF11, SAP8, DOT4, ZCF15, orf19.1219, and orf19.6713, representing 10% of the mutants screened, that were unable to illicit the Dar response, previously described as a robust disease phenotypes in C. elegans ( Figure S4A), in particular, a deformity in the post anal region (Dar) (Jain et al 2009).…”

New Role for DCR-1/Dicer in Caenorhabditis elegans Innate Immunity against the Highly Virulent Bacterium Bacillus thuringiensis DB27

“…Once activated, these pathways induce the expression of an array of antimicrobial effectors that differ, depending on the pathogen present (8)(9)(10)(11). A variety of microbes, including bacteria (12), fungi (13), viruses (14), and microsporidia (15), have been used in C. elegans infection studies, with the main focus on etiological agents of human diseases. In some cases, work on C. elegans has led to the identification of conserved virulence factors of human pathogens (16,17).…”