D-091. Characterizing a Role for Caenorhabditis elegans CUB-Like Domain-Containing Proteins in Immunity toward Yersinia pestis

D. D. Bolz, J. L. Tenor, K. L. Styer, A. Aballay;
Duke Univ., Durham, NC.

Caenorhabditis elegans is a genetically tractable organism that lacks a highly developed adaptive immune system and relies upon a conserved innate immune response to prolong survival during infection with pathogenic organisms. In the laboratory, C. elegans can be infected with mammalian pathogens allowing the nematode to be used to study host-pathogen interaction and identify conserved factors of innate immunity. In the present study, the C. elegans response to Yersinia pestis was investigated using microarray analysis to identify factors that protect the nematode from Y. pestis-induced lethality. Genes encoding a family of proteins containing a CUB-like domain were notably enriched in the upregulated cluster of genes during an early stage of infection. The high level of induction and enrichment of genes encoding the CUB-like family of proteins led us to hypothesize that these proteins participate in C. elegans immunity. Using a fluorescent reporter for the most highly upregulated member of the CUB-like gene family, F35E12.5, we found that additional pathogens, including P. aeruginosa and Y. enterocolitica, also highly induce expression of F35E12.5 during infection. Conversely, pathogens such as S. enterica and E. coli do not induce F35E12.5 expression demonstrating specificity in the induction of this family of genes in response to pathogens by C. elegans. Further, the fluorescent reporter confirmed that induction of F35E12.5 by Y. pestis was regulated by PMK-1, a homologue of mammalian p38 MAP kinase important to C. elegans immunity. Intriguingly, despite pathogen-specific induction and regulation by PMK-1, RNAi-mediated suppression of the most highly induced genes encoding members of the CUB-like family of proteins did not affect C. elegans survival during infection with Y. pestis. The lack of an RNAi-mediated phenotype during infection supports redundancy of function among the CUB-like family of proteins or redundancy through separate immunity pathways. Further investigation of the induction and regulation of these genes will help to determine a role for the CUB-like family of proteins in C. elegans immunity.