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C. elegans host response and the study of host/pathogen interactions

Posted by Lefteris on 30 Dec 2006 at 11:02 GMT

The article by Kerry et al. provides the opportunity to discuss two important topics: The use of invertebrates as model hosts to study microbial pathogenesis and the innate immune responses of C. elegans.

Over the last 10-15 years, the discovery of substantial commonality between virulence factors required for disease in mice and these non-mammalian model hosts has provide unique insights in microbial pathogenesis There are numerous examples that support the hypothesis that a common, fundamental set of molecular mechanisms is employed by pathogens against a widely divergent array of metazoan hosts. Especially, C. elegans can be used to study established and identify novel virulence determinants in a remarkably large number of human pathogens including Pseudomonas aeruginosa, Burkholderia pseudomallei, Burkholderia cepacia, Serratia marcescens, Salmonella enterica, Yersinia pestis, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Cryptococcus neoformans.

C. elegans does not possess a complete Toll pathway, but structural homologs of some components of this pathway, such as tol-1, trf-1, pik-1 and ikb-1, do exist (Pujol et al. Curr Biol 11 (11): 809-21, 2001). A genetic screen was curved out to identify components of a presumptive C. elegans innate immune response pathway upstream of induced defense responses. This led to the discovery that a C. elegans homologue of the mammalian p38 mitogen activated protein kinase (MAPK) is required in the immune response and is an important component of an apparent C. elegans defense response to pathogens (Kim et al. Science 297 (5581): 623-6, 2002). C. elegans does have a TIR (Toll-interleukin 1 receptor) that is a positive regulator of the antimicrobial peptide NLP 31, a member of the neuropeptide-like protein family. Purified NLP 31 demonstrated antifungal activity toward Drechmeria coniospora, Neurospora crassa, and Aspergillus fumigatus. C. elegans is more susceptible to D. coniospora when TIR-1 is silenced via RNAi (Couillault et al. Nat Immunol 5 (5): 488-94, 2004 and Liberati et al. Proc Natl Acad Sci U S A 101 (17): 6593-8, 2004).

Do you believe that the study of C. elegans host response can improve our understanding of mammalian host/pathogen interaction? How far can the nematode model take us in the study of microbial pathogenesis?