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Our laboratories have studied the mechanisms of aging (1, 2) and immune function (3) in Caenorhabditis elegans. Herein we show that the mechanisms that govern these two processes may be interrelated.
The human Gram-negative bacterial pathogens Pseudomonas aeruginosa and Salmonella enterica and the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus kill C. elegans by an infection-like process with remarkable overlap between the bacterial factors required for virulence in mammals and killing in nematodes (4, 5). Additionally, a p38 MAPK (mitogen-activated protein kinase) signaling cascade is a key component of the C. elegans innate immune response, as it is in mammals (3). These experiments establish C. elegans as a useful model for studying bacterial pathogenicity and host immunity. Here we show that certain long-lived C. elegans mutants are highly resistant to killing by bacterial pathogens.
To investigate the general relation between longevity and pathogen resistance, we tested whether C. elegans daf-2 and age-1 mutants exhibit enhanced resistance to E. faecalis, S. aureus, and P. aeruginosa. daf-2 encodes an insulin-like receptor that functions upstream of the phosphatidylinositol 3-kinase (PI 3-kinase) encoded by age-1, and partial loss of function mutations in daf-2 or age-1 result in a long-lived phenotype (1). Both daf-2 and age-1 mutants were resistant to killing by E. faecalis, S. aureus, and P. aeruginosa (Fig. 1A; table S1). Most dramatic was the five- and sixfold increased survival of the daf-2(e1370) mutants relative to wild-type C. elegans when exposed to the Gram-positive pathogens E. faecalis and S. aureus, respectively (Fig....