In the daf-2;dbl-1 double mutants, there is prolongation of longevity compared with dbl-1, with reduction GSK1904529A price in bacterial load. The phenotypic interaction between the DAF-2 and DBL-1 pathways indicates both playing roles in controlling bacterial load, with consequent effects on longevity. Role of downstream immune effector molecules on C. elegans longevity and intestinal bacterial load Since DAF-16 is BKM120 cell line involved in regulating several

antimicrobial proteins and antioxidant enzymes expressed in the intestinal tract [37, 38], we next addressed the role of the downstream effector molecules. C. elegans has 15 genes that encode lysozymes and 23 genes encoding saposin-like domains, of which lys-7, lys-8 and spp-1 are regulated by the DAF-2 pathway [31, 39–41]. Intestinal bacterial loads selleck inhibitor in lys-7 and spp-1 mutants were not significantly different from those in N2, but both mutants had significantly decreased lifespan when grown on both the E. coli and Salmonella

lawns (Table 1). For lys-1, regulated by both the p38 MAP kinase and TGF-β pathways, mutants have significantly shortened lifespans (Table 1). These results (Figure 5A and 5B; Table 1) indicate the importance of the encoded antimicrobial proteins in regulating lifespan, however, reduction in numbers of colonizing bacteria does not appear to be the sole mechanism for lifespan variation. Figure 5 Role of downstream components of the innate immunity pathways on intestinal bacterial proliferation and C. elegans lifespan. Survival of C. elegans mutants with defective expression of antimicrobial peptides (Panel A) or oxidative stress enzymes (Panel C) when grown on lawns of E. coli OP50. Panel B: Intestinal load of E. coli OP50 (dark bars) or S. typhimurium SL1344 (grey bars) with altered intestinal expression of antimicrobial peptides or oxidative stress enzymes (Panel D) on day 2 (L4 stage + 2 days) of their lifespan. Data represent Mean ± SD from experiments involving 30 worms/group. Significant (p < 0.05) differences in proliferation either

E. coli or Salmonella compared to N2 worms indicated by *. When ingesting bacterial cells, C. elegans also produce reactive oxygen species (ROS) [42]. The extreme resistance of daf-2 mutants to bacterial accumulation may depend on oxidative stress response proteins [42]. To explore this relationship, Tacrolimus (FK506) we studied worms with mutations of sod-3, encoding the anti-oxidant superoxide dismutase [43], or of ctl-2, a peroxisomal catalase [44]. The ctl-2 mutants had significantly decreased lifespan after exposure to either E. coli or Salmonella, and had significantly higher Salmonella density. In contrast, mutations in sod-3 had no effect on either lifespan or bacterial load (Figure 5C and 5D; Table 1). Thioredoxin is involved in maintaining reduced states inside cells [45], and is involved in immune response regulation as well, by controlling NFκB and AP-1 binding [46]. The C.