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|Session Title: Pathogenesis Session Type: Parallel|
|Session Location: Sunset Village Study Lounge Session Time: TUE June 28, 2005 09:00AM - 12:00NOON|
|Program Number: 294 Presentation Time: 9:40AM|
|Keywords: KW70 - Innate immunity|
Identification of new innate immunity genes. Anne Millet,
Nathalie Pujol, Jonathan Ewbank. Centre d’Immunologie de
Marseille-Luminy, INSERM/CNRS/Univ. de la Méditerranée, Marseille,
Infection of worms by bacterial or fungal infection causes the induction of specific response genes (1, 2). These include members of the nlp and cnc/caenacin families of antimicrobial peptide genes. We have focused on two genes, nlp-31 and nlp-29. Judged by GFP-reporter constructs, both are expressed in the hypodermis and are induced within four hours of infection with the fungus Drechmeria coniospora. Interestingly, the two genes show a cell-specific expression, such that only nlp-29 is strongly expressed in perivulval cells where fungal spores attach.
We have constructed a transgenic strain containing two integrated reporter constructs. The first, pcol-12::dsRed gives constitutive red fluorescence in the hypodermis and the second, pnlp-29::GFP is induced upon fungal infection. This has allowed us to investigate the specificity of the response to infection, using the Union Biometrica COPAS sorter to quantify reporter gene expression. We found that pnlp-29::GFP is not induced by a range of other pathogens nor by stresses such as starvation heat-shock or heavy metal exposure. Consistent with this, the induction of pnlp-29::GFP does not require kgb-1 or jkk-1 activity. It is in part dependent upon the activity of a MAPK pathway (that includes NSY-1 and SEK-1) and the TIR-domain adapter protein TIR-1 (2,3). This pathway also has a role in neuronal cell fate determination, acting downstream of unc-43 (4). But unc-43 mutants exhibit normal expression of pnlp-29::GFP, and it is not known what lies upstream of tir-1 in the nlp-activation pathway. Indeed, it is not known how infection is recognised in C. elegans.
We therefore conducted an EMS screen to identify mutants that do not express pnlp-29::GFP following infection with D. coniospora. None of the isolated alleles map to regions that contain genes known to be involved in innate immunity. Through SNP mapping, we have narrowed down the localisation of two alleles to distinct regions of the X chromosome, within an interval of some 200 genes. Progress on the identification of these genes will be reported.
1. Mallo et al. Curr Biol 12, 1209 (2002). 2. Couillault et al. Nat Immunol 5, 488 (2004). 3. Liberati et al. PNAS 101, 6593 (2004). 4. Chuang & Bargmann Genes Dev 19, 270 (2005).
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